Drug Pipeline and Pharmaceutical Market Data

Takeda's Ads To Tout Safety Of Diabetes Drug Actos

2007-11-15T12:34:00.000-08:00

Takeda Pharmaceutical Co. (4502.TO) plans to launch print ads Friday touting the safety of its diabetes drug Actos, just days after the U.S. Food and Drug Administration slapped new safety warnings on rival drug Avandia, from GlaxoSmithKline plc. (GSK).

Full-page ads set to run in about 60 newspapers and in several news magazines in the U.S. tell patients: "If you have type 2 diabetes, Actos has been shown to lower blood sugar without increasing your risk of having a heart attack or stroke," according to a copy of the ad provided by Takeda.

The FDA handed Takeda this marketing edge Wednesday, when it forced Glaxo to add a new warning to Avandia's prescribing label about potential heart attack risks for patients taking the drug. The FDA also said it would ask makers of other diabetes drugs, including Takeda, to note in their labels that their drugs haven't been proven to reduce cardiovascular risk.

Takeda, based in Japan, has tried to turn that into an advantage in the ads, telling consumers that Actos at least doesn't increase their risk of having a heart attack or stroke. The ad notes that a "major study" showed that Actos did not increase this risk in patients.

Shay Weisbrich, general manager of diabetes marketing at Takeda, said the company is concerned that the Avandia controversy has scared some patients off oral diabetes drugs altogether. "The more media there is out there, the more confusing it is for patients. We designed (the ads) to cut through that and provide some clarity," she said.

Some doctors have been switching their patients to Actos from Avandia in recent months, as concerns about Avandia's safety have mounted. Avandia's troubles began in May, when a prominent cardiologist published a study saying that patients taking Avandia had a higher chance of suffering a heart attack than those taking placebo or other oral diabetes medications. Glaxo has always maintained that Avandia is as safe for the heart as other oral diabetes drugs.

Actos is the only other marketed drug that works in the same way as Avandia. Before concerns about Avandia surfaced, the two drugs' sales were running neck and neck in the U.S. By midsummer, Actos sales were soaring while Avandia sales were plummeting. Ms. Weisbrich declined to say how Actos is selling currently.

Japan Group Aiming To Test AIDS Vaccine In US In 2010

2007-10-09T04:39:00.000-07:00

A Japanese consortium plans to begin clinical testing of its AIDS vaccine in the U.S. and elsewhere as early as 2010 in what would mark the first such testing of a Japanese-developed AIDS vaccine, The Nikkei reported in its Tuesday morning edition.

Developed using the proprietary technology of biotech venture firm Dnavec Corp., the nasal-spray vaccine is aimed at increasing the number of immune cells available to attack cells infected by HIV, the virus that causes AIDS.

The consortium includes the University of Tokyo, Dnavec, and the National Institute of Infectious Diseases, among others.

By using the vaccine, people who do not have AIDS would be able to increase their chance of fighting off the disease and reduce the risk of passing it on to others.

In tests that the group conducted using monkeys, HIV did not propagate among 60% of subjects given the vaccine prior to being exposed to the virus. Various AIDS vaccines have been tested around the world, but only a few were found to be effective in tests using monkeys, which belong to the same primate family as humans.

Clinical tests involving several dozen healthy people are expected to be organized through the International AIDS Vaccine Initiative, or IAVI, according to a basic agreement that has been struck with the Japanese group. If the tests prove the vaccine's safety and effectiveness, larger scale clinical tests will be carried out. The consortium hopes to commercialize the vaccine around 2015.

The IAVI, a global organization working to promote the development of preventative AIDS vaccines, is financed by donors including a foundation set up by Microsoft Corp. Chairman Bill Gates.

Switch From Lipitor To Generic Ups Heart Risks

2007-09-13T05:25:00.001-07:00

Switching patients from Pfizer Inc.'s (PFE) cholesterol drug Lipitor to a generic version of Merck & Co Inc.'s (MRK) Zocor has been linked to a 30% increase in the risk of major heart complications, according to a Pfizer-sponsored study.

The study was presented Wednesday at the European Society of Cardiology meeting in Vienna, Austria, and is due to be published in the British Journal of Cardiology.

The study was based on an analysis of a database of more than 11,000 U.K. patients which included records from October 1997 to June 2005.

The analysis compared 2,522 patients who had taken Lipitor for six months or more and were switched to Zocor, which is generically known as simvastatin, with 9,009 patients who remained on Lipitor therapy.

According to the study, patients who switched cholesterol treatment had 30% higher risk of death, heart attack, stroke and heart surgery than those who continued taking Lipitor.

Zocor and Lipitor belong to a class of drugs called statins, used to lower cholesterol levels in people with, or at risk of, cardiovascular disease.

"It's not beneficial to have a universal switch to cheaper statins," said study author Peter Lansberg, of the Academic Medical Centre, University of Amsterdam, The Netherlands.

"We need to make a distinction between patients who benefit from generic statins and high-risk patients who need a more aggressive therapy."

The launch of generic copies of Zocor, which lost patent protection in June last year, has hurt Lipitor sales as health insurers have been encouraging patients to switch to the cheaper cholesterol-lowering drug.

In 2006, Lipitor sales reached $12.9 billion, making it the top-selling drug of all time and a key product for New York-based Pfizer in the last decade.

However, in the second quarter of 2007, the company's profit fell 48% on the back of slowing Lipitor prescriptions, whose global sales fell 13% compared with the same period in 2006.

The decline was steeper in the U.S., where sales slid 25% to $2.7 billion in the second quarter.

Iressa Near To Sanofi's Taxotere In Lung Cancer

2007-09-13T05:24:00.000-07:00

Lung-cancer patients who took AstraZeneca PLC's (AZN) Iressa drug lived about as long as those taking Sanofi-Aventis's (SNY) Taxotere chemotherapy, according to a new study.

AstraZeneca said Wednesday the late-stage study compared overall survival between Iressa and Taxotere in 1,466 patients with advanced, non-small cell lung cancer who had received previous treatment.

The study showed Iressa was "non-inferior" to Taxotere. AstraZeneca said it was the first time a drug in Iressa's category has proven non-inferiority for overall survival, relative to chemotherapy, in a head-to-head Phase 3 study in patients with previously treated non-small cell lung cancer.

The data were presented at the World Conference on Lung Cancer in Korea. AstraZeneca didn't provide specific survival figures in a press release.

AstraZeneca also said Iressa had a more favorable "tolerability profile" and "superior quality of life" for patients, versus Taxotere.

Iressa is a type of targeted therapy known as an epidermal growth factor receptor tyrosine kinase inhibitor. AstraZeneca initially had high hopes for the drug but they were dashed when a study in 2004 showed that Iressa failed to extend lives in lung cancer patients. The U.S. Food and Drug Administration subsequently restricted use of the drug to people who are benefiting or have benefited from it. Iressa has been shown, however, to be effective in treating Asians with lung cancer.

Iressa is available in 36 countries, but not in most major European countries. Global sales were $113 million for the first six months of 2007. Taxotere sales were EU402 million in the first half of the year.

AstraZeneca said it's sharing the latest data with regulatory agencies.

J&J Ends Plan To Seek Wider Procrit Use

2007-09-13T05:23:00.000-07:00

Johnson & Johnson called off plans to seek a broader list of approved uses for its drug Procrit, after the drug failed to show a reduction in the need for red-blood-cell transfusions among critically ill patients.

The finding, published today in the New England Journal of Medicine, is the latest blow to Procrit and other forms of erythropoietin, or EPO, a hormone that stimulates red-blood-cell production and is used widely in cancer, kidney and HIV patients.

In March, J&J added a prominent notice to Procrit's label, warning of an increased risk of death, heart attacks, and tumor growth in some situations, after studies indicated such risks. Next week, a Food and Drug Administration panel will hold a hearing on risks to kidney patients. Procrit sales have fallen 21% from two years ago.

The FDA has approved Procrit to treat anemic patients going into surgery or chemotherapy, and those who have kidney failure or HIV. J&J wanted to broaden that list to include anemic patients in an intensive-care unit, irrespective of a particular disease.

In the study, which J&J funded, doctors enrolled 1,460 ICU patients. Half received three injections of Procrit over a 15-day period, and the other half received a placebo.

A previous J&J study, published in 2002, suggested Procrit would reduce the need for red-blood-cell transfusions, but the latest study didn't show a reduction. As a result, J&J is calling off its attempt to broaden the drug's approved uses, a spokeswoman said.

Doctors are allowed to prescribe Procrit in the intensive-care unit anyway, but few do, said Aryeh Shander, the chief of the department of anesthesiology and critical-care medicine at the Englewood Hospital in Englewood, N.J. Today's study is likely to decrease such "off-label" use, said Dr. Shander, who has received grants and consulting fees from J&J.

In today's study, Procrit patients showed a drop in deaths, but the result wasn't statistically significant. Procrit did increase the risk of blood clots and other "thrombotic vascular" events, by roughly 40%, confirming the FDA's warnings and previous studies.

Procrit is made by Amgen Inc., which gets a 10% royalty from J&J. It sells the same drug to kidney patients undergoing dialysis as Epogen. J&J also sells a different synthetic erythropoietin, Eprex, internationally. J&J sold $758 million of Procrit and Eprex in the quarter ended in June.

Mylan Laboratories Says FDA Approves Carvedilol Tablets

2007-09-13T05:22:00.000-07:00

Mylan Laboratories Inc. (MYL) said Thursday its Mylan Pharmaceuticals Inc. unit received Food and Drug Administration approval for its Abbreviated New Drug Application for carvedilol tablets.

Carvedilol is the generic for GlaxoSmithKline PLC's (GSK) Coreg tablets.

Mylan, a Canonsburg, Pa. drug company, said about $1.65 billion of the tablets were sold in the U.S. in the year ending June 30.

Teva Gets OK To Sell Generic Protonix, Though It May Wait

2007-09-13T05:20:00.000-07:00

Though Teva Pharmaceutical Industries Ltd. (TEVA) won the right to sell a generic version of Wyeth's (WYE) Protonix, it remains unclear if it will actually move to launch the product immediately.

On Thursday, a federal court denied a preliminary motion to block Teva from launching a generic version of the treatment for erosive esophagitis associated with gastroesophageal reflux disease.

But complicating the matter is that the basis for the denial is unknown because the judge's opinion in the ruling, coming from the U.S. District Court for the District of New Jersey, was filed under seal pending review that it doesn't contain any confidential or proprietary information.

"Teva would obviously be much more willing to launch if the ruling was predicated on strong likelihood of success on the merits," writes Ken Cacciatore from Cowen & Co.

The full decision is expected to become available this coming Wednesday, according to a report from Bear Stearns.

"Teva intends to complete a thorough analysis of (Thursday's) decision before deciding upon its next course of action," the Israel company said in a statement.

Cacciatore said this is more cautionary language than usual from Teva following a preliminary injunction victory.

"Our best guess without seeing the ruling is that Teva and Wyeth may now reach a settlement and/or Teva will wait for a decision at trial," he said.

Though obviously, if the ruling does contain strong language on the merits of Teva's rationale for challenging the patent, then it may move to launch immediately.

Such a move is known as an "at-risk" launch because the generic maker can later be compelled to pay substantial damages to the branded-drug companies if their patent is upheld in court.

In its own statement, Wyeth said the court emphasized that its findings were preliminary and that the generic companies "would need to meet a higher burden of proof, clear and convincing evidence."

The court determined that Teva had raised sufficient questions about the validity of the patent to preclude issuance of the "extraordinary remedy" of a preliminary injunction, the Madison, N.J., company said.

Wyeth and Altana Pharma AG, recently acquired by Nycomed, sued Teva and Sun Pharmaceutical Industries Ltd. (524715.BY) for alleged patent infringement based on Teva's and Sun's filing of Abbreviated New Drug Applications seeking Food and Drug Administration approval to market generic Protonix before the patent expires July 19, 2010.

Under the Hatch-Waxman Act, the filing of the lawsuit stayed final FDA approval of Teva's ANDA until Aug. 2, 2007, and Sun's ANDA until Saturday.

Teva received that approval, but agreed not to launch before a decision was issued on Wyeth's motion for a preliminary injunction to prevent the launch until the resolution of the lawsuit.

Teva will have a 180-day period of marketing exclusivity, which will begin to run from the date of first commercial marketing or a final court decision.

A trial date has not been set.

Protonix was Wyeth's third-best-selling product in 2006, with $1.8 billion in sales. Wyeth licenses the drug from Nycomed.

Aspreva, Roche Won't Submit CellCept Reg Filings

2007-09-12T12:34:00.000-07:00

Aspreva Pharmaceuticals Corp. (ASPV) and Roche Holdings AG will not submit regulatory filings for using the drug CellCept to treat lupus nephritis because its Phase III trial showed the drug was not "superior" to another treatment.

The Victoria, B.C., pharmaceutical company Aspreva said the trial compared CellCelpt, an immunosuppresant, with intravenous cyclophosphamide to treat the disease, which causes swelling of the kidneys.

The disease is caused by a malfunction of the immune system, which, if suppressed, can relieve symptoms.

Insights And Items Of Interest From Other Sources

2007-07-12T11:32:00.000-07:00

Biotech's Future Could Reside in the Home

The enormous potential of biotechnology won't be realized by large corporations making new crops, but by companies aiming at homes and small farms, says physicist Freeman Dyson.

Biotechnology will enter into individuals' daily lives in the 21st century much in the same way that electronic devices like personal computers and digital cameras brought the advances in physics and chemistry into the homes of the late 20th century, Dr. Dyson says.

In the early computer era, pioneers like John von Neumann wrongly assumed computers would develop into "large centralized facilities." Similarly, people today generally think of genetic engineering as the exclusive domain of large corporations. Instead, Dr. Dyson says, biotechnology will make its largest advances by becoming "small and domesticated." For centuries, people have been effectively genetically engineering plants and animals through selective breeding. As individuals gain access to the tools of biotechnology, they will expand the diversity of pets and plants for recreational purposes, even creating games that allow children to tinker with genes, competing to make the prickliest cactus or scariest lizard. Genetically modified tropical fish with new colors already are appearing in pet stores.

Beyond household fun, Dr. Dyson, the father of information-technology guru Esther Dyson, anticipates that the domesticated form of biotechnology will allow rural communities to challenge the economic power of cities, by transforming themselves into biotechnology research centers. He notes that Dolly, the first cloned sheep, came from an animal-breeding center in Scotland, rather than Silicon Valley. With their expertise in biotechnology, rural communities might even come up with technologies for heavy industry, such as developing earthworms that could wring aluminum from clay or seaweed that could extract magnesium from sea water.

Dr. Dyson, known for making bold predictions in many scientific fields and a favorite source for science-fiction writers, says biotechnology still poses many dangers. He leaves it to future generations to resolve how his futuristic vision can be safely adopted.

Radiate Study Meets Primary End Point

2007-07-12T11:26:00.000-07:00

Swiss drugmaker Roche Holding AG (RHHBY) said Tuesday that RADIATE, the third study in Actemra's (tocilizumab) extensive multinational phase III development programme, successfully met its primary endpoint.

The study examined Actemra in combination with methotrexate in rheumatoid arthritis (RA) patients who had an inadequate response to anti-tumour necrosis factor therapy (anti-TNFs).

The study conducted in 498 patients with difficult-to-treat RA disease, showed that a greater proportion of patients treated with Actemra plus methotrexate, achieved a significant improvement in disease signs and symptoms (ACR scores3) following 24 weeks of treatment, compared to patients treated with placebo plus methotrexate.

"RADIATE's positive outcome further confirms the critical role of IL-6 in the pathophysiology of rheumatoid arthritis," said Urs Schleuniger, Business Director, Inflammation and Autoimmune Disease, Roche Pharmaceuticals. "These results add to the wealth of data being compiled ahead of the anticipated regulatory filing later this year," he added.

Roche In $1B Alliance With Alnylam On RNAi

2007-07-12T11:24:00.000-07:00

Roche Holding AG (RHHBY) Monday entered an alliance worth up to $1 billion with Alnylam Pharmaceuticals Inc. (ALNY) of the U.S. in which the Swiss drugmaker obtains access to the U.S. biopharmaceutical company's technology platform for developing treatments based on RNA interference.

Roche, based in Basel, said it will pay Alnylam $331 million upfront, including a cash payment and an equity investment of $42.5 million, which represents a stake of just under 5% of Alnylam's outstanding shares.

The close of the agreements, including Roche's purchase of Alnylam shares and purchase of Alnylam's site in Germany, is subject to certain regulatory approvals and is expected within around 30 days.

RNA interference, or RNAi, is considered one of the hottest new areas of drug research. It represents breakthrough in understanding how genes are turned on and off in cells. RNAi was the basis for last year's Nobel Prize in medicine, as it is seen offering a completely new approach to drug discovery and development.

Roche's deal follows on the heels of AstraZeneca's (AZN) deal with U.K.-based Silence Therapeutics Plc (SLN.LN), announced on Friday and valued at as much as GBP200 million. Last fall, Merck & Co. (MRK) agreed to pay $1.1 billion for Sirna Theruapeutics Inc. of the U.S. to get access to RNAi technology.

Santhera And Novartis Set Licencing Deal On CMD Treatment

2007-07-09T07:55:00.001-07:00

Switzerland-based Santhera Pharmaceuticals AG (SANN.EB) Monday said it has enetered a licensing agreement with Novartis AG (NVS) covering the compound omigapil for the treatment of Congenital Muscular Dystrophy, or CMD.

Santhera will pay Novartis an upfront fee, and a further milestone payment upon entering into the pivotal clinical trial in CMD. Santhera will have the right to use all preclinical and clinical data generated on omigapil and receives the remaining drug substance on stock at Novartis. Furthermore, Novartis will receive an additional payment if the drug receives market approval in the EU and the United States as well as royalties based on the sales of the product.

Santhera will develop omigapil as a potential treatment for this severe, genetically determined neuromuscular condition which frequently affects infants or young children with life-threatening progressive muscle weakness. Santhera expects to commence a Phase II trial in CMD patients by the end of 2008. Santhera also has the option to expand the development of omigapil into other neuromuscular indications while Novartis retains a buy-back option confirming Novartis' continuing interest in the compound and its potential as identified by Santhera.

Novartis retains the option to buy back the rights to omigapil under certain conditions. If Novartis decides to exercise this buy back option Santhera would be reimbursed a multiple of its development costs and would receive milestone payments upon market approval as well as royalties based on future product sales. In addition, Novartis is committed to use Santhera's specialized sales and marketing organization in the U.S., which is expected to be in place to support the launch and marketing of Santhera's lead compound SNT-MC17 for Friedreich's Ataxia and other indications.

Santhera will need to perform additional preclinical development work with SNT-317, given its intended use in children, before commencing a Phase II clinical trial in CMD patients. This trial is expected to start before the end of 2008.

Galapagos Extends Osteoarthritis Deal With GlaxoSmithKline

2007-07-09T07:53:00.000-07:00

Galapagos NV (GLPG.BT) announced Monday that its existing multiyear alliance in osteoarthritis with GlaxoSmithKline (GSK) will be expanded, and that Galapagos has issued 513,281 new shares for an investment of EUR4.4 million by GSK.

GSK will bring a drug discovery program against a selected GSK target into the alliance. Within this additional program, Galapagos will progress a disease-modifying drug towards completion of clinical Phase IIa or "Proof-of-Concept", at which point GSK's global research and development organization will be responsible for the late-stage development, production and marketing of the drug. Furthermore, GSK may add a second osteoarthritis drug discovery program against a selected GSK target into the alliance.

Industries and Government Promote E-Prescribing

2007-07-09T07:49:00.000-07:00

The widespread use of electronic systems to send prescriptions from doctors to pharmacies promises to prevent thousands of life-threatening medical errors, save billions of dollars in health-care costs and even drive more business to drug stores.

Most U.S. physicians, however, have yet to adopt electronic prescribing, or e-prescribing, for the estimated 4 billion prescriptions they write annually, a situation that a phalanx of corporations and the government are working to change.

E-prescriptions, at only a couple of million a month today, "are on the verge of an explosion," Walgreen Co. (WAG) Chairman David Bernauer told the National Association of Chain Drug Stores in April.

With e-prescribing, physicians can use hand-held or desktop computers or "smart" mobile phones to send patient drug prescriptions to pharmacy computers.

Beyond conveying prescriptions, systems can alert doctors to potential drug interactions or dosing problems, eliminate handwriting errors, automate the time-consuming renewal process, provide data on a patient's drug plan, and potentially cut thousands of pharmacy calls to doctors. Hospitals, insurers, technology companies, regional collaboratives and pharmacies have been working to advance adoption of e-prescribing.

The drug store industry formed an organization, SureScripts, in 2001 to develop a network that now allows doctors to electronically transmit prescriptions to almost all U.S. pharmacies. More than 120 physician and pharmacy software companies are certified or nearly certified to send or receive prescriptions over the SureScripts exchange.

The scores of physician software companies with products used in e-prescribing include large electronic health-records businesses such as General Electric Co.'s (GE) GE Healthcare and standalone e-prescribing concerns such as Zix Corp. (ZIXI).

Early this year, one of those companies, clinical software maker Allscripts Inc. (MDRX), joined computer maker Dell Inc. (DELL) to form a broad coalition - the National ePrescribing Patient Safety Initiative - in a $100 million effort to provide for free Allscripts' Web-based e-prescribing technology to every physician in the U.S.

The NEPSI coalition includes health insurers Aetna Inc. (AET) and WellPoint Inc. (WLP), technology giants Microsoft Corp. (MSFT) and Cisco Systems Inc. (CSCO), Fujitsu Ltd.'s (FJTSY) U.S. computer business, Google Inc. (GOOG), Sprint Nextel Corp. (S), SureScripts, Wolters Kluwer N.V.'s (WTKWY) health division, and several academic medical centers.

The coalition targets doctors in small group practices, aiming to address concerns about costs and difficulty, among other barriers to their adoption of e-prescribing technology.

"A doctor can sign up within an hour," Allscripts Chief Executive Glen Tullman, co-chair of NEPSI, said in an interview. The coalition isn't providing statistics yet but Tullman said the effort is "making great progress."

NEPSI estimates that as many as 20% of the 550,000 practicing U.S. physicians had the technology to send e-prescriptions but that only 5% of the nation's doctors actually have been using it to prescribe electronically.

Allscripts' Tullman said the coalition's effort so far has added thousands of more physicians nationwide to the ranks of e-prescribers. He expects "a very strong, very high-visibility" ramping up in September, with large employers and more managed-care companies and payors joining the coalition. He also expects state governments to become active in mandating electronic prescribing.

After recent updates to state laws and regulations, e-prescribing is now legal in 49 states and soon will become so in all 50 with the addition of Alaska, according to SureScripts President and Chief Executive Kevin Hutchinson.

E-prescribing proponents, including the U.S. Department of Health and Human Services, point to a study that estimates adoption of e-prescribing technology could save $27 billion in U.S. health-care costs by reducing adverse drug events and improving work flow.

"Clean and correct scripts safeguard our patients' safety, save our pharmacists time and increase our business," Walgreens' Bernauer said in his speech. Bernauer cited a study showing that 11% more prescriptions make it to the pharmacy when a doctor switches to e-prescribing.

HHS, in a recent report to Congress, cited expert projections that e-prescribing could avoid more than 2 million adverse drug events annually, 130,000 of which are life-threatening. Even so, five government-funded e-prescribing pilot projects did not establish the effect on patient safety, the report said, noting the role of office staff members in handling e-prescribing tasks. The effect on safety requires more study, the report said.

The Allscripts-Dell coalition cites statistics from the nonprofit Institute of Medicine of the National Academies that 1.5 million patients a year are injured and more than 7,000 die as the result of preventable medication errors. The numbers actually may be higher, as Allscripts says studies indicate that doctors using the NEPSI-provided software cancel 1% of prescriptions because of improper-dosage or adverse-reaction warnings during prescribing.

Investment firm Stifel Nicolaus expects the move to e-prescriptions to accelerate in the near term, and sees its adoption as "a key on-ramp to the adoption of electronic medical records," a view that some others share.

E-prescribing is a component of insurer WellPoint's multi-million-dollar health information-technology efforts, said Charles Kennedy, WellPoint vice president for health IT. In Ohio, doctors can earn higher reimbursement from WellPoint if they fill prescriptions electronically.

WellPoint sees e-prescribing as a way to lower costs and improve safety and quality of care, including driving greater use of generic drugs, Kennedy said. The company is seeing very rapid growth in the transactions, although e-prescribing, in its early stages, remains "a drop in the bucket," he said.

Allscripts is "doing the right thing" and making health-care better in giving doctors free access to its web-based e-prescribing software, Allscripts CEO Tullman said. He acknowledged that the company also aims to build its brand and sell its wider offering of electronic-health-records software to physicians. "We think of this as the on-ramp to the electronic health-care highway," he said.

The company estimates that its paying customers and those receiving the free software account for approximately half of all prescriptions filled electronically in the U.S. today.

Among other efforts in recent years, regional partnerships in Massachusetts, where Blue Cross and Blue Shield of Massachusetts is involved, and Rhode Island have made those states e-prescribing leaders. In Michigan, the big three U.S. automakers joined with insurers and others to launch an e-prescribing effort.

Researchers from the Center for Studying Health System Change noted in the journal Health Affairs this spring that physicians with e-prescribing equipment reported various problems with using it but said employment of such technology improves prescribing safety and the efficiency of their practices, "and they did not want to go back to paper."

The Medicare Modernization Act of 2003 required adoption of technical standards for processing electronic prescriptions and mandated that Medicare prescription-drug plans support e-prescribing.

The law effectively resolved industry debate over which standards to use, according to SureScripts CEO Hutchinson. He also serves as a commissioner on HHS's American Health Information Community, which develops standards to accelerate adoption of health-care technology.

E-prescribing is one process the federal government is exploring to improve health-care interoperability and keeping patients on their medications, he said. The prescription "makes it beyond the glove box of the car," Hutchinson noted.

Dr. Jan Cornell, a family practice physician in Calumet, Mich., adopted Allscripts' free software in February. "The pharmacists were really happy to see me use something that has a printout," he said. The initial loading of patient information into the system can be a chore, and his colleagues are wary of the task, he said.

NICE OKs Elan, Biogen MS Treatment Tysabri

2007-07-05T10:36:00.001-07:00

Ireland-based Elan Corp. (ELN) and U.S.-based Biogen Idec (BIIB) said Tuesday they welcome the U.K. National Institute for Health and Clinical Excellence recommendation for the use of their drug Tysabri, the first NICE approval for any multiple sclerosis drug.

The companies said Tysabri represents a significant advance in MS treatment, offering hope of delaying the progression of disability and reducing the frequency of relapses.

According to the companies, treatment with Tysabri over two years leads to a 68% relative reduction in clinical relapses and a 54% relative reduction in the risk of sustained disability progression compared with placebo.

As of late May, the treatment was being used in about 12,000 patients in both commercial use and clinical trials in the U.S., Germany, France, Ireland and other countries.

However, said one analyst who follows the sector, a key approval for the drug is still awaited from the U.S. Food and Drug Administration.

"This has to be seen in that context," he said, though he added that approval in the U.K. clearly bodes well for the drug.

Roche's Actemra Clears Hurdle On Way To Approvals

2007-06-22T08:27:00.000-07:00

Drugmaker Roche Holding AG (RHHBY) Friday said Actemra, an experimental drug that treats rheumatoid arthritis in a new way, showed positive results and was safe in a key study, paving the way to file the drug for regulatory approval in Europe and the U.S. later this year.

Roche, based in Basel, Switzerland, said the study, dubbed OPTION, showed that a greater proportion of patients treated with Actemra in combination with traditional drugs achieved a significant improvement in disease signs and symptoms after 24 weeks, compared to those treated with the traditional drugs alone.

Sufferers of rheumatoid arthritis, or RA, begin to experience progressive joint damage early in the disease. The disease differs from what is popularly known as arthritis, typically associated with age-related joint pain; RA is a far more serious inflammatory disease that leads to destruction of cartilage and bone, and can lead to disability.

Patients have a big number of treatment options to chose from, but many drugs merely relieve pain, in some cases at the cost of severe long-term side effects including osteoporosis and high blood pressure.

Actemra works by inhibiting the activity of interleukin-6, a protein that plays a major role in the inflammation process of rheumatoid arthritis; it's generally well tolerated, Roche said.

If approved, Actemra will compete with other biological drugs called anti-TNF medicines. These medicines target a compound known as tumor necrosis factor, which is overproduced in many patients with inflammatory disease.

Johnson & Johnson's (JNJ) Remicade and the drug Enbrel, which is co-marketed by Amgen Inc. (AMGN) and Wyeth (WYE), are all part of this class.

In the study, four times the number of patients in the Actemra group experienced a 50% improvement in disease symptoms compared to the control group, while more than ten times the number of Actemra patients achieved 70% improvement in disease signs and symptoms compared to the control group. In addition, 28% of patients achieved the ultimate goal of remission in the Actemra group against only 1% of patients in the control group.

At 0950 GMT, Roche shares were up CHF1.60, or 0.7%, at CHF219.90, in a higher broader market.

Actemra, also known as tocilizumab, was developed by Japanese pharmaceutical company Chugai Pharmaceutical Co. (4519.TO), which is controlled by Roche. Roche owns the rights to market Actemra outside Japan.

The drug has shown very good results in trials conducted in Japan, and Roche hopes to replicate these early data from the Japanese trial in large American and European studies. The study presented Friday, is is the first of five international late-stage trials that are investigating Actemra's efficacy and safety.

Roche plans to file Actemra for regulatory approval in Europe and the U.S. by the end of 2007. It usually takes around a year for regulators to review data submitted by a company and decide on approving a new drug.

In Japan, where the approval process usually takes somewhat longer, Actemra was filed for regulatory approval in April 2006.

Gilead Says FDA Approves Drug To Treat PAH

2007-06-22T08:25:00.000-07:00

Gilead Sciences Inc. (GILD) said the U.S. Food and Drug Administration late Friday approved its drug ambrisentan for the treatment of a lethal form of hypertension that strikes without warning and can kill within three years if untreated.

The drug, which will carry the U.S. trade name Letairis, is designed to treat a disease known as pulmonary arterial hypertension (PAH), in which arteries in the lungs constrict and thicken, raising blood pressure and eventually causing heart failure. Patients typically go to doctors complaining of exhaustion, breathlessness, and inability to walk distances or perform activities of normal daily living. Often no cause can be identified, although the condition also can be triggered by diseases like scleroderma or advanced HIV, or by certain medicines like the diet drug combo Fen-Phen.

Letairis belongs to a class of drugs called ERAs or endothelin receptor antagonists, compounds that relax the vessels, lowering blood pressure and lightening the load on the heart and lungs. However, such drugs can't be taken by pregnant women due to risk of major birth defects, and can cause liver damage.

In studies, the drug improved patients exercise capacity, as measured by a six-minute walking distance test. Gilead said it has priced the drug at $3,940 a month, comparable with other oral drugs for the disease. Gilead said it established a program to ensure greater access to patients who are underinsured or face high co-payment requirements.

Because of the risks of liver damage and birth defects, the drug's label will carry strong cautionary language in a black box, as do other drugs of its class. Gilead says its studies show that incidence of liver damage is less with Letairis than with other products in this class. The company said Letairis will be available only through a special restricted program to educate patients and doctors about safe usage.

Gilead acquired the drug as a result of its merger with the drug's developer Myogen Inc. in November 2006, and plans to make it the centerpiece of a third branch of its business in the cardio-pulmonary field. Gilead's core business has focused mainly on products for HIV and hepatitis.

Based on market research, Gilead said it estimates about 75,000 to 90,000 people in the U.S. suffer from PAH, and 200,000 people worldwide, although fewer than half of them are currently believed to be diagnosed. The condition is often misdiagnosed as exercise-induced asthma or other respiratory ailments.

Letairis will be marketed in the U.S. by Gilead, and by GlaxoSmithKline PLC (GSK) outside the U.S.

Basilea Superbug Filed For European Approval

2007-06-22T08:23:00.000-07:00

Basilea Pharmaceutica AG (BSLN.EB) said Monday its superbug antibiotic has been submitted for European approval, prompting a milestone payment of 12 million Swiss Francs ($9.8 million) for the Basel-based company.

Basilea said the anti-infective treatment ceftobiprole was submitted to the European Medicines Agency by a subsidiary of Johnson & Johnson (JNJ), with whom Basilea will sell the treatment in the U.S. and major European countries.

"Today's marketing authorization application submission as well as the recent new drug application filing in the USA reflect our view that ceftobiprole could play an important role globally in the future management of important medical problems posed by methicillin-resistant Staphylococcus aureus," Basilea's Chief Executive Anthony Man said in a statement.

The filing, in keeping with Basilea's pledge to submit the treatment this year, follows favorable study date from January, where the treatment was shown to be effective against complicated skin infections.

In January, Basilea said ceftobiprole demonstrated high cure rates in a range of patients, including those with methicillin-resistant Staphylococcus aureus, or MRSA, and diabetics with foot infections.

Basilea shares, which jumped earlier this year after the most recent data from ceftobiprole, have gained 28% this year, giving the company a market capitalization of $2 billion.

The stock closed at CHF272 Friday; trading resumes at 0700 GMT Monday.

Ceftobiprole is in Phase-III testing to treat patients who develop pneumonia while in hospital, as well as community-acquired pneumonia, for which Basilea expects results in the latter half of 2007.

New Option For Rare Condition

2007-06-22T08:22:00.000-07:00

People with a rare and lethal high blood pressure now have more options for convenient treatment with less drug toxicity.

Late Friday the Food and Drug Administration approved Letairis, a pill made by Gilead Sciences Inc. for the treatment of pulmonary arterial hypertension, in which lung vessels constrict, raising blood pressure and leading to heart failure.

Mysterious and often misdiagnosed, PAH can arise without warning. It also can result from diseases like scleroderma or advanced HIV, or the diet drug combo known as fen-phen. Based on market research, Gilead, of Foster City, Calif., estimates 75,000 to 90,000 people in the U.S. have PAH, over half of them undiagnosed.

About a half-dozen PAH drugs exist, all of them expensive, including round-the-clock infusions and some oral drugs that risk birth defects and liver damage. Some patients require lung transplants, though drug therapy can stave off the need for it. Letairis's label carries a black-box warning about such risks, but the company and some analysts say it has the best safety profile of any oral drug to date. Shashi Sahgal, a 42-year-old homemaker and mother of two teenagers in Mission Viejo, Calif., was hiking and bounding up stairs two at a time back in 2002. When she felt winded, doctors thought she had exercise-induced asthma. By the end of 2002, exhaustion and an enlarged heart led doctors to perform a right-heart catheterization. That nailed the diagnosis of PAH.

Without treatment, PAH can be fatal within three years. Referred to lung specialist Ronald Oudiz of Harbor UCLA Medical Center in Torrance, Calif., Mrs. Sahgal entered a trial of the new Gilead drug, then known by its generic name ambrisentan. "It made a huge difference," she says.

Gilead acquired ambrisentan as part of its merger with Myogen Inc. last November, and it now plans to launch sales in the U.S. this week. Under a co-marketing agreement with GlaxoSmithKline PLC, GSK is seeking approval to market the drug outside the U.S. On Friday, the FDA delayed action on another PAH drug, Thelin by Encysive Pharmaceuticals Inc. of Houston, urging more studies.

The first drug approved for the condition in 1995 was GSK's Flolan, an infusion given continuously through a chest catheter. Originally designed as a bridge to a transplant, the drug treatment alone has extended some of his patients' lives by 13 or 14 years, says UCLA's Dr. Oudiz. Gilead now sells Flolan in the U.S., while GSK markets it outside the US.

United Therapeutics Corp., Silver Spring, Md., markets a similar drug, Remodulin, which is given as a subcutaneous or intravenous infusion. A pill form is being studied.

Swiss drug maker Actelion Ltd. markets an inhaled drug, Ventavis. It also markets a pill, Tracleer, part of an oral-drug family that expands vessels but can cause liver damage or birth defects.

Gilead's Letairis is also part of the same drug family, known as ERAs (endothelin receptor antagonists, which work by relaxing blood vessels). Gilead says its studies show Letairis has a lower incidence of liver toxicity than rival products. Common side effects include peripheral edema (or swelling), nasal congestion, flushing and palpitations. Patients must have liver enzymes monitored to detect any signs of damage, and women -- who account for most PAH patients -- must avoid becoming pregnant.

Pfizer Inc. entered the field after discovering its erectile-dysfunction drug, Viagra, could benefit vessels of the lungs as well. The New York company rechristened the drug as Revatio for PAH. Another such drug, Indianapolis-based Eli Lilly & Co.'s Cialis, is now in tests for PAH.

Like other orphan drugs for rare but serious diseases, PAH treatment is costly. A year of Flolan can run $100,000, while Tracleer tops $40,000, according to Gilead officials.

On Friday, Gilead said it set the price of Letairis at $3,940 a month, or $47,280 a year, using Tracleer's pricetag as a benchmark. The company plans to offer patient assistance with reimbursement, as well as some discounts and free drugs to patients lacking coverage.

A year of Revatio given as a thrice-daily 20-milligram tablet is about $10,000, says Dr. Oudiz. But for uninsured patients who are taking higher doses, he says it is less costly to take the drug as Viagra.

Dr. Oudiz has received funding support from Actelion, Gilead, Pfizer, United Therapeutics, Encysive and Lilly.

Like many patients who move to combination therapy, Mrs. Sahgal now also takes Revatio, along with the blood-thinner coumadin to prevent clots.

"I still can't go uphill fast, and I'm not going to climb Mt. Everest," says Mrs. Sahgal, now 46. But she adds, "If all goes well, we're looking at 20-plus years."

BioMS Gets FDA Approval For Pivotal Trial Of MS Drug

2007-01-22T13:42:00.000-08:00

BioMS Medical Corp. (MS.T) has received approval from the U.S. Food and Drug Administration to start a pivotal trial of its lead drug, MBP8298, a potential treatment for patients with secondary progressive multiple sclerosis, the company confirmed.

The Phase III trial will enroll about 510 patients and take about two years, said Kevin Giese, BioMS Medical's president and chief executive.

The company has already begun a Phase III trial of the drug in Canada and Europe, which will enroll about 550 patients.

Multiple sclerosis is a disease of the central nervous system, marked by such things as paralysis, blindness and cognitive impairment.

Shares of BioMS are halted in Toronto Friday. The stock last traded at C$3.48.

Kevin Giese, president and chief executive of BioMS Medical Corp. (MS.T), said the company submitted an application for the trial with the U.S. Food and Drug Administration last month, and the agency gave its consent relatively quickly.

That means BioMS will soon have two Phase III trials in secondary progressive multiple sclerosis, or MS.

He hopes to commence the U.S. trial, which will cost a total of about C$50 million, in the first half of this year. While the company does have the funds to initiate the study, it will eventually have to raise more to get it done, he added.

Giese also noted that the Alberta-based biotech is close to completing patient enrollment in the Canada/Europe MS trial, and that data from an interim analysis of the trial are due 16 months from now, which isn't that far off in biotech terms. This trial has passed six safety reviews by an independent board to date.

Geron Spinal Cord Treatment Produces Nerve Growth

2007-01-22T13:41:00.000-08:00

Geron Corp. (GERN) said Wednesday its stem-cell treatment for spinal-cord injuries produced nerve growth in animal models, potentially removing a first hurdle for it to begin clinical trials in the future.

Shares of the company were recently trading up 29 cents, or 3.4%, at $8.94, on heavy early volume.

Menlo Park, Calif.-based Geron said Wednesday findings for the treatment, GRNOPC1, affirmed the company's cell-based approach to spinal-cord injury.

When injected into animal models, the therapeutic stimulated nerve growth and extension, in addition to its already reported remyelinating activity - which repairs the coating around the neurons without which nerves are unable to function.

"The multiple functions of GRNOPC1 affirm the potential therapeutic utility of our cell-based approach to the repair of spinal cord injury and provide multiple mechanisms within a single therapy to achieve functional recovery," said Thomas B. Okarma, Geron's president and chief executive officer.

Geron operates at a loss, and recently reported its third-quarter loss narrowed to $9.84 million, or 15 cents a share, from $11.9 million, or 21 cents a share, in the year-earlier period.

But research advances are lending hope to doctors that spinal-cord injuries will one day be treatable.

"They are on the road to entering the clinic and this is the first step for that to proceed," said WBB Securities analyst Stephen Brozak, who had no conflicts to report.

The treatment could improve survival of the neurons, and allow formation of alternative circuitry, where they have been disrupted due to spinal-cord injury. Return of sensation would markedly improve quality of life, Brozak said.

Although stem-cell research has been inhibited by federal legislation in the U.S., shares of Geron and other companies recently received a lift after an approved constitutional amendment in the state of Missouri was passed protecting the research, and amid hopes a Democrat-controlled House of Representatives will be more amenable towards the field.

There are an estimated 10,000 to 12,000 spinal-cord injuries in the U.S. every year, and a quarter of a million Americans currently live with spinal-cord injuries, most of those being under 30 years old.

FDA Approves Shire Drug For Ulcerative Colitis

2007-01-22T13:39:00.000-08:00

The Food and Drug Administration has approved a new Shire PLC (SHPGY) drug to treat mild to moderate ulcerative colitis, the company said Tuesday.

The drug, Lialda, is a once-daily formulation of mesalamine, a drug commonly used to treat the condition.

Ulcerative colitis is a type of inflammatory bowel disease, a chronic condition that causes inflammation of the digestive tract. It's believed that about 500,000 Americans have ulcerative colitis.

Mike Yasick, Shire's senior vice president who oversees gastrointestinal drugs, said Lialda will offer much more convenient dosing than other mesalamine pills, which include another Shire drug, Pantasa. Those drugs require dosing three to four times daily and six to 16 pills.

A survey released last month by the Crohn's and Colitis Foundation of America found that 65% of patients with ulcerative colitis aren't compliant with their medication, which can make the disease more difficult to control.

Shire said Lialda would be available during the first quarter of this year.

More serious cases of ulcerative colitis are treated with steroids and other medications, such as Johnson and Johnson's (JNJ) Remicade, designed to block a protein involved with the inflammatory process.

OraSure Sees Oral Hepatitis C Test Trials Ending In 2007

2007-01-17T03:46:00.000-08:00

OraSure Technologies Inc.'s (OSUR) chief executive Thursday said he expects clinical trials of a rapid oral test for the detection of hepatitis C to be completed by the end of this year.

Once the trials of the test - being jointly developed by OraSure and Schering-Plough Corp. (SGP) - are completed, the company will apply for marketing approval in the U.S., and in Europe soon thereafter.

Last week, Schering-Plough and Bethlehem,Pa.-based OraSure - which already makes the only approved HIV rapid oral test - inked a two-year deal to jointly develop and market the oral hepatitis C test.

The CEO also said OraSure was looking globally to acquire companies with complementary product profiles and with new technologies related to the treatment of infectious diseases.

"We have $90 million in cash right now and are looking to deploy it," Michels said. "We are actively evaluating potential acquisitions and technology-licensing agreements."

Michels said the development of novel treatments for hepatitis C that cut down on treatment time would be a boost to the market's acceptance of the company's test.

Vertex Pharmaceuticals Inc. (VRTX) is engaged in developing such a therapy, as is Schering-Plough, which makes the current standard treatment for hepatitis C, pegylated interferon, called Peg-Intron, which is often used with ribavirin.

The hepatitis C virus is the most common blood-borne infection in the U.S., with around 4 million people suffering from it. It affects as many as 170 million people worldwide. It is the main reason for liver transplants in the U.S.

Michels said as many as 2 million to 3 million Americans who may have the virus remain untested.

While new infection rates have declined in the U.S., and blood is now screened for the virus, those who caught it through blood transfusions in the late 1970s and early 1980s are approaching treatment age, and many more in the population may have the virus but remain unchecked as symptoms can take up to 20 years to appear.

Basilea Shares Jump On Positive Test Results

2007-01-17T03:45:00.000-08:00

Shares in Basilea Pharmaceutica AG (BSLN.EB) hit record highs Wednesday after the Swiss biotechnology company said late-stage testing of its superbug antibiotic ceftobiprole showed it to be effective in treating complicated skin infections.

The Basel-based company said ceftobiprole demonstrated high cure rates in a range of patients, including those with methicillin-resistant Staphylococcus aureus, or MRSA, and diabetics with foot infections. Basilea also said it plans to submit its first regulatory filing for the drug this year.

Analysts said the positive results weren't a surprise, given that the drug had already been proven successful in an earlier late-stage study, but are still good news for the company.

"A good outcome was expected, but this trial was perceived as slightly riskier than earlier ones, so this (outcome) is nice," said Denise Anderson, an analyst at Kepler Equities, who believes ceftobiprole will become best-selling antibiotic globally with annual sales of at least $1B.

Still, Anderson doesn't plan to change her estimates following the latest trial data, noting the stock is already generously valued. She has a reduce rating on Basilea with a CHF170 target price.

At 0953 GMT, shares in Basilea, which plans to jointly sell ceftobiprole with Johnson & Johnson (JNJ) unit Cilag GmbH International in North America and major European countries, were up 3.1% at CHF220.50 - off its earlier record high of CHF221.90 - in a lower Swiss market.

Basilea said 91% of clinically evaluable patients in the Phase III trial were cured with ceftobiprole, compared to 90% of patients treated with combination therapy.

The clinical response in patients with diabetic foot infections was 86% for ceftobiprole and 82% for comparator combination therapy, respectively.

Over 20% of microbiologically evaluable patients had confirmed MRSA infections. The cure rate for ceftobiprole in MRSA patients was 91% compared to 86% for the comparator regimen.

One third of patients had infections involving a Gram-negative pathogen. The microbiologic eradication rates in these patients were similar at 84% in both treatment groups. Markus Metzger, an analyst at Bank Vontobel, said in a note he expects ceftobiprole to hit the market in 2008. He noted the revenue potential of the antibiotic also depends on the results of testing against another condition.

"Ceftobiprole is reflected in our estimates with a peak sales potential of CHF1.5 billion...across all indications, with the potential to a large part being dependent on the second indication," hospital-acquired pneumoniae, or HAP, he said.

Results from that trial are expected during the second half of 2007, he added. Metzger's price target for Basilea's stock remains at CHF188.

Bacteria such as MRSA have developed resistance to conventional antibiotics in recent decades as major pharmaceutical companies have focused on treatments for chronic lifestyle diseases and new cancer therapies, leaving research to small biotech companies.

Basilea, which listed on the Swiss stock market in March 2004, first signed an agreement with Johnson & Johnson to develop, manufacture and sell ceftobiprole in early 2005. As part of the agreement, the Swiss company would get upfront and milestone payments of up to CHF370 million. It would also get double-digit royalties on worldwide sales if the MRSA drug made it to the market.

volutec Open To Offers As Key Drug Fails Test

2007-01-17T03:44:00.000-08:00

Biopharmaceutical company Evolutec Group PLC (EVC.LN) said it would be open to sale offers Wednesday after its key development drug rEV131 failed to produce results in a key trial.

Chief Financial Officer Nicholas Badman said the trial result means all options are on the table, including a potential sale of the company: "Someone may seek to take the whole company," he said, adding: "We are very much open to all routes."

Badman's comments follow an earlier announcement by the company that in a Phase II trial on reducing allergic inflammation after cataract surgery rEV131 performed the same as a placebo.

At 0930 GMT the shares were down 3.5 pence or 18% at 14.75 pence, leaving the company with a market value below GBP4 million. The group listed in August 2004 at 125 pence per share.

The compound rEV131 was being tested as a treatment to combat inflammation after post-cataract surgery, but the company's statement Wednesday said the trial found "no significant differences" between rEV131 and the placebo.

In December Evolutec's shares slumped 70% in a day's trading after negative results using rEV131 to treat hay fever were announced. Evolutec is now scrapping investment in the drug. However it is pursuing another compound, rEV576, which it says has shown potential in therapy for myasthenia gravis and Guillain-Barre Syndrome.

The CFO would not say whether the company has received any expressions of interest, or whether it has approached potential buyers, nor would he give a timeline for a potential sale of the company: "There is no time line but we are going to actively pursue [options], we will do whatever."

The CFO said the group has enough cash for the foreseeable future and that the company is undervalued: "We're worth a lot more than our current share price suggests, we've got the cash and there's a lot of potential value in rEV576."

Nomura Code analyst Gary Waanders said the trial result leaves little value in the company: "This was the supporting indication for their lead product, that's gone now so there's not much in their pipeline of any real value," Waanders said, adding: "It's pretty hard to see where they might go from here."

Waanders highlighted that the group is trading at a discount to its cash reserves of GBP8.7 million or 33 pence per share, and said it may be a target for a biotechnology company looking to top up its cash.

The analyst does not have a rating on the company.

The compound rEV131 had been touted as a potential blockbuster, and in October the group raised GBP2.8 million to fund the trials of the drug.

The Reading, UK based company's drugs are based on compounds found in the saliva of blood-feeding ticks. Ticks can remain undetected on their hosts for weeks and the company's products aim to use compounds to treat allergic, autoimmune and inflammatory diseases.

The company's only other pipeline drug, rEV576 is at the preclinical stage of trials for its use as a treatment against muscle weakness, or myasthenia gravis. It is also being tested as a treatment for Guillain-Barre Syndrome, a nerve system disorder and against asthma and heart attack.

Feedback needed

2006-12-23T14:11:00.000-08:00

If you like our blog and the information we provide and you are interested in more information or a report referring to pharmaceuticals and pharmaceutical industry, don't hesitate to contact us at support@chartsbank.com or simply leave us a comment, we will be glad to publish this information or if it is of extreme value, provide you with necessary details about the expenses.

Bulresearch is a leading provider of market research inormation!

Merry Christmas to all and God bless you!

Neopharm Stock Slumps; Cancer Drug Falls Short Of Hopes

2006-12-12T11:26:00.000-08:00

Neopharm Inc. shares slumped 75%, to a 52-week low, after the company announced that its experimental drug for brain cancer didn't perform statistically better in a clinical trial than an existing drug.

The stock was trading recently at $1.73, off $4.99 from Friday's close at $6.72. Earlier, the shares fell to $1.68, off $5.04 from Friday's close and surpassing a previous 52-week low of $4.32 set in July.

Volume was 10.4 million shares traded, compared with a daily average of 426,000.

Analysts called the sell-off warranted.

"It's a very fair reaction," said Brean Murray Carret & Co. analyst Jonathan Aschoff, who noted that he had a sell rating on Neopharm shares prior to Monday's development.

Aschoff said he thinks shares of Neopharm, a Waukegan, Ill., pharmaceutical company, are worth "a couple bucks," or a slight premium to the company's cash.

Neopharm's drug - cintredekin besudotox - "did not beat the control" in the study, Aschoff said. "It was slightly better, but no where near statistically so."

ThinkEquity Partners analyst Vinny Jindal said it's unclear what the company will do now.

Jindal described the investor reaction as "largely justified," and he said he plans to listen closely to a Neopharm conference call that's been scheduled for after Monday's market close to see "how (company executives) plan to put Humpty Dumpty back together again."

Drug Pipeline Series: Submissions, Dec 4 - Dec 11, 2006

2006-12-12T10:49:00.000-08:00

Theravance, Inc. announced that it submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for telavancin, a rapidly bactericidal injectable antibiotic with a unique multifunctional mechanism of action, for the treatment of complicated skin and skin structure infections (cSSSI) caused by Gram-positive bacteria.

Eli Lilly and Company announced that it submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration's Division of Drug Oncology Products (DDOP) for EVISTA® (raloxifene HCl) for the reduction in risk of invasive breast cancer in postmenopausal women with osteoporosis and postmenopausal women at high risk for breast cancer. EVISTA is currently indicated for the treatment and prevention of osteoporosis in postmenopausal women.

Drug Pipeline Series: Phase III, Dec 4 - Dec 11, 2006

2006-12-12T10:37:00.000-08:00

Isotechnika Inc. announced that the Company has enrolled its first patient in a pivotal Phase III European/Canadian clinical trial for the treatment of moderate to severe psoriasis with its lead immunosuppressive drug, ISA247.

Vanda Pharmaceuticals Inc. announced positive top-line results from the company's Phase III clinical trial evaluating iloperidone, an atypical antipsychotic, in patients with schizophrenia.

Drug Pipeline Series: Phase II, Dec 4 - Dec 11, 2006

2006-12-12T10:31:00.000-08:00

Helix BioPharma Corp. announced that it has initiated patient enrollment in a Phase II clinical trial of Topical Interferon Alpha-2b for the treatment of ano-genital warts (condylomata accuminata) associated with human papilloma virus ("HPV") infection. The trial, which is taking place in Sweden, will assess the efficacy and safety of Topical Interferon Alpha-2b compared with placebo using a double blind, randomized design over an examination period of four months per patient.

Immtech Pharmaceuticals, Inc. announced that it has initiated a Phase II trial in the U.S. of its oral drug candidate, pafuramidine maleate, as a prophylaxis to prevent malaria infections for travelers to endemic regions. This study protocol was reviewed by the U.S. Food & Drug Administration and has been approved by the Institutional Review Board of a major U.S. medial center. It is estimated that each year 125 million travelers go to countries where malaria is endemic.

MethylGene Inc. , along with its partner Pharmion Corporation announced the initiation of a Phase II clinical trial with its isotype-specific histone deacetylase (HDAC) inhibitor product candidate, MGCD0103, in patients with high-risk myelodysplastic syndromes (MDS) or relapsed or refractory acute myelogenous leukemia (AML). Specific patient populations include elderly patients who have previously untreated disease or adult patients who have relapsed or refractory disease.

Cleveland BioLabs has begun a Phase II efficacy study of Curaxin CBLC102 in advanced, hormone-refractory (androgen independent) prostate cancer.
Curaxin CBLC102 is an oral drug used in the past to treat malaria that demonstrates efficacy in vitro, in animal models and in live tumors removed from patients. Initial test results indicate that CBLC102 can be effective against a number of malignancies, including hormone refractory prostate cancer, renal-cell carcinoma and soft-tissue sarcoma.

Solvay Pharmaceuticals, Inc., Wyeth Pharmaceuticals, a division of Wyeth and Lundbeck A/S presented clinical study results for bifeprunox at a major medical conference this week. Bifeprunox is an investigational treatment for schizophrenia studied as a once-daily regimen. Results of these efficacy and safety studies showed that, in a six-month trial, bifeprunox maintained stability in patients with stable schizophrenia versus placebo.

EPIX Pharmaceuticals, Inc. announced the initiation of a Phase 2a clinical trial to further evaluate PRX-03140 as monotherapy and in combination with donepezil for the treatment of Alzheimer's disease. This Phase 2a trial is designed to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of PRX-03140 administered orally once-daily for 14 days in patients with mild Alzheimer's disease who are on a stable dose of donepezil (10 mg). Data from this trial are expected in the second half of 2007.

Inspire Pharmaceuticals, Inc. announced the initiation of a Phase 2 clinical trial to evaluate epinastine nasal spray for the treatment of seasonal allergic rhinitis.
This Phase 2 clinical trial is a 14-day randomized, double-blind comparison of two doses of epinastine nasal spray (0.05% and 0.1%) to placebo in approximately 580 subjects who have a documented history of seasonal allergic rhinitis to mountain cedar pollen.

Drug Pipeline Series, Phase I, 4 Dec - 11 Dec, 2006

2006-12-12T10:29:00.000-08:00

Nastech Announces Positive Phase 1 Clinical Results of Insulin Nasal Spray Compared to Exubera® Inhalation Powder and NovoLog(C) Insulin Aspart Injection.

Vernalis plc announced that it has started a Phase I trial of V24343, a CB1 antagonist, as a potential treatment for obesity, type II diabetes and related disorders.

Neose Technologies Presents Positive NE-180 Phase I Clinical Trial Data at American Society of Hematology Annual Meeting, a Novel GlycoPEGylated™ Erythropoietin, Demonstrates Dose-Dependent Activity in a Phase 1, Single Dose, Dose Escalation Study in Normal Human Volunteers". NE-180 is being developed for the treatment of anemia associated with chronic kidney disease, including patients on dialysis and patients not on dialysis, and for the treatment of anemia in adult cancer patients with non-myeloid malignancies receiving chemotherapy.

OMRIX Biopharmaceuticals Commences Phase 1 Clinical Trial for Fibrin Patch product for the management and rapid control of bleeding including severe bleeding in surgery.

ArQule, Inc. announced the enrollment and successful dosing of the first patient in a Phase 1 clinical trial with ARQ 171, a second-generation compound generated through its Activated Checkpoint Therapy(SM) (ACT) program. Phase 1 data from this compound, together with Phase 2 data from the ongoing ARQ 501 program, will form the basis of a future licensing decision by Hoffmann-La Roche (Roche).

Merck & Co., Inc. and Vertex Pharmaceuticals Incorporated announced results of a Phase I clinical trial for MK-0457 (also known as VX-680), an investigational small molecule inhibitor of Aurora, FLT-3, JAK-2 and BCR-ABL kinases. The study, conducted at The University of Texas M. D. Anderson Cancer Center and Duke University Medical Center, showed that MK-0457 demonstrated clinical activity in select patients with chronic myelogenous leukemia (CML) and Philadelphia chromosome-positive acute lymphocytic leukemia (Ph+ ALL) with the T315I BCR- ABL mutation and also in patients with refractory JAK-2 positive myeloproliferative diseases (MPD).

Novacea, Inc. announced that Phase 1 data of AQ4N (banoxantrone), an investigational anti-cancer prodrug, demonstrated that AQ4N was active and well tolerated when administered to patients with non-Hodgkin's, chronic lymphocytic and Hodgkin's lymphomas.

Dynavax Technologies Corporation announced the initiation of a Phase 1 dose escalation clinical trial of its TLR9 agonist in combination with a standard chemotherapeutic regimen for metastatic colorectal cancer. The enrollment target of the trial is 15 patients, all of whom will have been previously treated for colorectal cancer but had a recurrence of the disease.

Avigen, Inc. announced findings from a Phase I clinical trial for AV650 (tolperisone), an oral therapy intended for the treatment of disabling neuromuscular spasticity and spasm. AV650, a New Chemical Entity (NCE) in the U.S., was found to be well tolerated with no evidence of sedation in this trial.
The Phase I study enrolled 30 healthy adult volunteers at one center in the U.S.

DURECT Corporation announced that it has successfully completed Phase I clinical trials with a new product, DUR-843, which is intended to treat a persistent pain condition. We believe that the persistent pain market remains underserved and that DUR-843 has the potential to provide several advantages over existing pain medications.

Nuvelo Hit As Drug Fails In Trial

2006-12-11T11:20:00.000-08:00

Shares of Nuvelo Inc. (NUVO) plummeted 80% to $3.97 before the opening bell Monday after the company and partner Bayer AG (BAY) said a Phase III clinical trial of its blood clot dissolving drug didn't meet its primary endpoint.

The drug, alfimeprase, used for treatment of thrombotic, or clot-related disorders, didn't meet its primary endpoint of avoidance of open vascular surgery within 30 days of treatment in patients with acute peripheral arterial occlusion, known as "leg attack," the company said Monday.

The companies also suspended enrollment in two other Phase III trials.

"While Nuvelo did not say exactly why the trials failed, we believe that it is safe to assume that there was almost nothing encouraging about the results of the trials," Brean Murray says, adding it expects deal with Bayer to dissolve.

Nuvelo and Bayer HealthCare have a global collaboration for the development of alfimeprase, whereby Bayer would bring it to market outside the U.S. and will pay Nuvelo tiered royalties, and Nuvelo retains marketing rights in the U.S.

American Depositary Shares of Bayer had yet to trade.

Shares of travel-booking company Sabre Holdings Corp. (TSG) rose 11% to $31.30 on news reports that the company is up for sale and could be sold to a new buyer as early as this week, at a premium to its $3.75 billion market capitalization.

Private-equity groups were viewed as the most likely purchasers of Sabre, the reports said. Citing people involved in the negotiations, The New York Times said the bidding group favored to win the auction includes Silver Lake Partners and Texas Pacific Group, while a rival bidding group is led by Apollo Group. The people involved in the talks said a third group of investors is also considering a bid, the Times said.

Shares of Biomet Inc. (BMET) rose 4.8% to $41.80 after a newspaper report said British company Smith & Nephew Ltd.(SN.LN) will this week make a GBP5 billion offer for the company, in an attempt to to create the world's fourth-largest orthopedic implants maker.

Biomet in effect put itself up for sale in April when it appointed Morgan Stanley (MS) to advise on strategic options, The Independent, a U.K. daily, said on its Web site.

Shares of DuPont Co. (DD) rose 0.7% to $47.25, after the company lifted its fourth-quarter outlook. DuPont also said it would close or change manufacturing processes at 10 of its sites and cut about 1,500 jobs worldwide.

DuPont now anticipates 2006 earnings of $3.25 a share, up from a previous outlook of $2.86 a share. The company said it would list additional benefits in the fourth quarter, including about $60 million from insurance payments from asbestos litigation and Hurricane Katrina-related claims and $500 million from tax adjustments.

Analysts polled by Thomson Financial presently forecast 2006 earnings, on average, of $2.88 a share.

Shares of DirectTV Group Inc. (DTV) rose 2.1% in pre-market trading to $24.80, after Deutsche Bank upped its rating on the company to buy, saying the digital television service provider is best positioned to take advantage of high-definition TV and will benefit from becoming part of the Liberty Media Corp. empire.

Shares of Cepheid (CPHD) rose 5.4% to $9.49 after the company received approval from the Food and Drug Administration to market its Smart GBS test for Group B Streptococcus on its SmartCycler platform.

Novartis Drug Tasigna Helps Leukemia Patients

2006-12-11T11:16:00.000-08:00

Swiss drugmaker Novartis AG (NVS) said Monday an intermediate stage study showed that its experimental drug Tasigna achieved impressive results in the treatment of blood cancer patients who no longer responded to treatment with its drug Gleevec.

The study showed that 74% of patients in the chronic phase of chronic myeloid leukemia, or CML, a blood cancer, achieved normal white blood cell counts after six months of treatment. Of 279 patients treated, the defective chromosome that causes the disease was significantly reduced in more than half, and was completely eliminated in about a third of these patients.

All these patients had developed resistance to Gleevec, the standard of care for the condition, or didn't tolerate Gleevec.

The study was presented at the American Society of Hematology, or ASH, meeting in Orlando, Florida.

Gleevec, launched five years ago and one of the first of what are known as targeted cancer drugs is Novartis' second-best selling drug with sales of $2.17 billion in 2005. Targeted cancer drugs work by killing cancer cells specifically, or by hindering their proliferation, while traditional chemotherapy often kills deranged and healthy cells alike, leading to troublesome side effects.

Tasigna, known generically as nilotinib, and Gleevec, known generically as imatinib, both work by telling a specific gene to stop producing excessive white blood cells. Tasigna was designed to also work in cases when this gene had mutated. Such mutations can cause resistance to the Gleevec treatment. CML patients usually go through three phases: chronic phase, accelerated phase and blast phase.

In 52% of patients in the chronic phase of CML, the Ph+ chromosome - the genetic abnormality that characterizes most cases of this form of leukemia - was significantly reduced, while in 34% it was undetectable after treatment with Tasigna, Novartis said.

Patients in a more advanced phase of CML also responded to the Tasigna therapy.

Of the 64 patients in the accelerated phase, 59% achieved a normalization of their white blood cell counts, and in 36% the Ph+ chromosome was reduced or eliminated after eight months of treatment.

The study researchers concluded that Tasigna was generally well tolerated. Specifically, the investigators said that the compound wasn't associated with many of the side effects seen with Gleevec, such as fluid retention and superficial edema.

Novartis, based in Basel, Switzerland has recently submitted Tasigna for U.S. and European Union regulatory approval, on the basis of this study. When considering cancer drugs, the regulators sometimes accept earlier phase II studies rather than larger phase III trials that it typically requires most companies to submit with drug-approval applications.

James Shannon, head of drug development at Novartis, said recently that he expects global peak sales of Gleevec and Tasigna combined to exceed $3.5 billion.

David Epstein, who heads Novartis' oncology business told an agency that the company plans to start a trial that directly compares Tasigna to Gleevec in the first half of 2007. Should Tasigna turn out to be more effective, as well as safer, in this trial, it could eventually replace Gleevec as the standard of care for this form of leukemia.

However, both Gleevec and Tasigna will also be competing with Sprycel, or dasatinib, a drug developed by Bristol-Myers Squibb Co. (BMY), which has been launched in both Europe and the U.S. this year.

Tasigna and Sprycel have never been tested against each other, which makes it difficult to compare them, but data so far suggest that the Novartis drug has less unwanted side effects, analysts say.

"Tasigna appears to be at least as effective as Sprycel, but with fewer side effects," said Karl-Heinz Koch, analyst in Zurich at private bank Vontobel, who has a buy rating on Novartis.

Bristol-Myers also presented data at the ASH conference, that are directly comparing Sprycel to a high dose of Gleevec, when given to patients who no longer responded to the standard Gleevec those.

After 15 months of treatment, the defective chromosome that causes CML was significantly reduced in 53% of patients who were given Sprycel, compared to 33% of patients who took the high dose of Gleevec.

"This study may help answer important questions about treating resistant chronic-phase CML patients and suggests that physicians should consider treatment with Sprycel in patients resistant to lower doses of Gleevec," said Neil Shah, an assistant professor at the division of hematology and oncology of the University of California, in a statement.

Still, given that these patients had already developed resistance to the standard dose of Gleevec, it shouldn't come as a huge surprise that Sprycel was shown to work better for these patients, Vontobel's Koch added.

Actelion about To Disclose New Cardiovascular Drug

2006-12-10T10:35:00.000-08:00

Swiss pharmaceutical company Actelion Ltd (ATLN.EB) will release details of a new experimental heart drug this month that most analysts say could be either a successor to its flagship drug Tracleer, or a new niche treatment.

Actelion has been tightlipped so far on the compound, dubbed Actelion-1, and has not revealed which specific disease the drug is aimed at. But in a survey of 10 analysts by an agency, five said Actelion-1 would probably be a specialty cardiovascular drug, while two thought it would likely be a follow-up to Tracleer. Three were undecided. Two of the analysts said they thought the compound could also be a diabetes-related drug.

Actelion is heavily dependent on revenue from Tracleer right now, and industry experts say a positive announcement regarding either an improved Tracleer follow-up or a wholly new drug could substantially boost the stock.

"It's either an improved follow-up to Tracleer or an innovative compound in the cardiovascular specialty area," said Birgit Kulhoff, an analyst at Rahn & Bodmer.

Actelion spokesman Roland Haefeli would only say, "We do expect to make a disclosure on Actelion-1 before the end of the year...it's a compound evaluated for cardiovascular diseases in Phase II testing."

Tracleer is used to treat pulmonary arterial hypertension, or PAH. The condition is rare but often fatal and causes arteries in the lungs to become narrow or blocked and blood pressure to rise.

Actelion derived around 95% of the CHF247.2 million (US$206.4 million) in sales it posted during the third quarter from the drug, which was the only available treatment for PAH when it was launched in 2001, though competition is now waiting in the wings.

Encysive Pharmaceuticals Inc.'s (ENCY) Thelin is expected to soon receive final U.S. approval, while Myogen Inc. (MYOG) - recently bought by Gilead Sciences Inc. (GILD) - is expected to file its ambrisentan drug soon.

Given Actelion's current dependence on Tracleer, some analysts said investors could respond more positively if Actelion-1 turns out to be a new specialty cardiovascular drug rather than a new version of Tracleer.

At 1310 GMT Friday, Actelion's shares were up 1.4% at CHF223 in a lower Swiss market.

"Positive results from (a trial on Actelion-1 and another trial on Tracleer) would...likely cause us to boost our target price, perhaps substantially," said Denise Anderson, an analyst at Kepler Equities who has a buy rating on the stock with a CHF255 target price.

Negative results would leave her estimates unchanged, and any dip in the share price would also be a good entry point, she added.

Of those pharmaceutical analysts expecting a Tracleer follow-up, one said it could be a more targeted compound and could therefore potentially be more effective or have a smaller risk of side effects.

"It's likely to be a follow-on compound to Tracleer," he said. "In order to make the secrecy around Actelion-1 economically sensible, the only thing I can come up with is that it's a selective endothelin antagonist."

An endothelin receptor antagonist works by blocking endothelin receptors, with which endothelin - responsible for constricting blood vessels and raising blood pressure - connects in order to be activated.

However, most analysts say they don't expect an updated version of Tracleer and note it's hard to predict with so little information available which heart conditions a cardiovascular drug might target.

"It's not going to be a hypertension drug as Actelion says it plans to market the drug themselves" and marketing a hypertension drug would involve collaboration with another company due to the higher costs involved, said Anderson at Kepler Equities. "And the number of cardiovascular indications that it could be, is huge," she added.

Auxilium Pharma Shares Dn On Disrupted Trial

2006-12-10T10:33:00.000-08:00

Auxilium Pharmaceuticals Inc. (AUXL) shares fell 8% Thursday after the company said it has to suspend dosing in a Phase III trial of a drug for the treatment of Dupuytren's contracture, a rare hand deformity, due to a manufacturing issue.

Dupuytren's contracture, which usually occurs in white adults in their 50s and 60s and is currently treated by surgery, can cause the fingers to bend towards the palm, and is caused by a thickening of the skin of the palm.

Late Tuesday, the company said it was temporarily stopping the dosing of patients in its ongoing Phase III trials for its AA4500 drug, and will conduct an investigation into the problems, which it believes are due to a higher-than-expected moisture content within some vials used to store the drug, possibly because of faulty equipment.

Shares of the company were recently changing hands at $14.68, down $1.28, or 8%, with around 1.3 million shares traded, more than three times average daily volume.

Auxilium's drug is unique in that it is a non-surgical approach. Currently there is no cure for the problem, and surgery doesn't prevent a recurrence. Injectable enzymes can break down the knots and cords of the hardened tissue.

The company said during a conference call that it has notified the U.S. Food and Drug Administration before re-starting the clinical trials and expected the FDA to take around 30 days to review the data. Management said it was uncertain whether it would have to create a new batch of drugs for the trials, adding investigators will continue to monitor patients already dosed in the trials.

Piper Jaffray said a delay could push back its launch timeline for late 2008, but may not have an impact on Auxilium's exclusivity for the drug, as Auxilium has orphan-drug protection - which is granted for drugs that treat rare diseases - for seven years in the U.S.

Iloperidone NDA Seen In 4Q 2007

2006-12-10T10:31:00.000-08:00

Vanda Pharmaceuticals Inc. (VNDA) said that its antipsychotic drug, iloperidone, performed well in a late-stage clinical trial, adding that a New Drug Application for it likely will be filed with federal regulators late next year.

Separately, Vanda Chief Executive Mihael Polymeropoulos said during a CNBC interview Thursday that various pharmaceutical companies have expressed interest in buying his company because of its pipeline of products.

The dual developments sent shares of Vanda, a Rockville, Md.-based biotech company, soaring to a 52-week high of $28.67 in early trading, up 85% from Wednesday's close and surpassing a previous 52-week high of $17 set Nov. 15.

The shares were trading recently at $26.31, up $10.81, or about 70%. Volume was 5.12 million shares traded, compared to a daily average of 312,000.

Vanda executives said the Phase III clinical trial evaluated iloperidone, an atypical antipsychotic, in patients with schizophrenia. The drug demonstrated statistically significant improvement compared to placebo on the Positive and Negative Symptom Scale, the trial's primary endpoint, they said.

Paolo Baroldi, Vanda's chief medical officer, said in a prepared statement that the successful trial means the company is getting closer to filing a New Drug Application for iloperidone with the Food and Drug Administration, which is expected in late 2007. The company also is "one step closer to making iloperidone available to patients and providers dealing with schizophrenia," Baroldi said.

JP Morgan concurred in a research note, saying the Phase III results are sufficient for the NDA filing expected in late 2007.

Meanwhile, Vanda's Polymeropoulos said during his CNBC interview that no decisions have been made regarding a possible sale of the company, although he said many suitors likely would be interested.

Microbicides Against HIV

2006-12-10T10:26:00.000-08:00

Women are increasingly at risk of contracting the HIV virus, and yet the most well-known method to prevent transmission during sexual activity is ultimately a decision made by the man.

But the days where male condoms are the best and easiest solution might be coming to an end as four different forms of microbicides - gels or creams with antivirals women can apply vaginally to prevent HIV (human immunodeficiency virus) infection - are now in final testing phases.

Experts say a total of more than 60 microbicides are in various stages of development and testing with some formulated as a pre-loaded diaphragm, cervical cap, sponge or vaginal ring releasing an active ingredient over time. The different microbicides include antivirals that use different methods of targeting the cells and virus.

"We know if there are more options, it's more likely to be used," said Anna Forbes, deputy director of the Global Campaign for Microbicides, a nonprofit organization based in Washington, D.C.

The first microbicide expected to complete testing is Carraguard, which is made from seaweed. It's being developed by the nonprofit Population Council in New York. Phase III trials are being conducted in three locations in South Africa and will be completed in March 2007.

Analysis of the data should be published by the end of 2007, and if Carraguard shows effectiveness at blocking HIV transmission, the council will seek the first regulatory approval from the South African Medicines Control Council. The council does intend to seek approval afterwards, if the data justifies it, by the U.S. Food & Drug Administration.

"Our goal is to develop a product used by women in the countries hardest hit by HIV and so we will work with regulatory entities in those countries," said Melissa May, director of public information for the council.

New Prophylactic

So far, Carraguard hasn't shown any significant side effects in testing on animals and humans, according to May.

"It's hard" for many of these women to persuade their partners to use condoms," May said. "Women really liked" the concept that they were in control with microbicides, she added. May noted that an additional benefit comes from the increased lubrication that the microbicides provide, a feature received positively both by men and women in testing.

Carraguard is currently being tested for use one hour before intercourse. But later testing and the subsequent versions of microbicides will be tested for use up to 24 hours or even on a monthly basis, according to Dr. Zeda Rosenberg, chief executive of the nonprofit International Partnership for Microbicides of Silver Spring, Md.

That would be a particular incentive for use in areas such as Darfur, where gang rapes are commonplace and a leading source for HIV transmission. Young girls could use microbicides as well, as rapes of children are on the rise. Subsequent microbicides are expected to be tested for effectiveness in blocking HIV transmission during anal sex.

The efficacy of first-generation microbicides is expected to range from 40% to 70%, with the lowest rate averting 18% of infections; and at 60% effectiveness, 35% of infections could be prevented. That could translate into countless lives being saved - more than 25 million people have died of AIDS since 1981, according to a recent report by the United Nations AIDS/World Health Organization. HIV causes AIDS (acquired immunodeficiency syndrome) by damaging white blood cells and other defenses against infection.

Currently, the only known way to spread the HIV virus is through the exchange of bodily fluids such as blood or semen from an infected person.

Cost-Effectiveness

Most versions of microbicides are coming from nonprofit organizations such as the Population Council and from small companies, such as Polydex Pharmaceuticals Ltd. (POLXF) of Canada. Pharmaceutical powerhouses such as Bristol-Myers Co. (BMY), Merck & Co. (MRK) and Johnson & Johnson (JNJ) are providing compounds for research as well.

It makes sense for the nonprofit organizations to take the leading role in the development of microbicides since they are better positioned to conduct trials in the developing world, according to John Moore, a professor of microbiology and immunology at Weill Medical College of Cornell University in New York. Moore has been working with Bristol-Myers and Merck on these projects.

Experts say that among the three compounds from the major companies, the Bristol-Myers and Merck versions stop the HIV virus from entering cells whereas the Johnson & Johnson compound - developed by its Tibotec subsidiary - stops replication of the virus.

TMC120, the Tibotec compound, is in a number of Phase I/II trials, according to Karen Manson, a spokeswoman for Tibotec, which is collaborating with the International Partnership for Microbicides.

The primary audience, at least initially, for microbicides are mostly women who live at the poverty level.

With antiviral therapy, "if it's not inexpensive," it won't be used, said Polly Harrison, director of the Alliance for Microbicide Development of Silver Spring, Md.

This could be very attractive for companies that are interested in "high-volume and low-margin products," the International Partnership for Microbicides' Rosenberg said.

The U.N. estimates that nearly 40 million people worldwide are currently living with HIV and AIDS, including 4.3 million newly infected in 2006. More than half of new infections are occurring in women. Research has shown that women are biologically more vulnerable to infections.

High-Profile Support

Meanwhile, 45 million new HIV infections are expected to occur between 2002 and 2010. Across sub-Saharan Africa, where the highest rates of infection are occurring, UNAIDS/WHO said that women between 15 and 24 years old are at least three times more likely to be HIV-positive than young men.

The dollar amounts targeted for microbicide research have grown tremendously amid public support from former President Bill Clinton, the Bill and Melinda Gates Foundation, the Rockefeller Foundation and others. Five years ago, much of the focus on HIV prevention was on finding a vaccine, but today many experts are more encouraged about the potential immediate impact of microbicides. In 1997, about $28 million was given to fund microbicide research; in 2005 that grew to $163 million.

In a Rockefeller Foundation report, estimates for the net present value of investing in a first-generation microbicide range from negative $65 million to negative $27 million. The second-generation product could be self-funding, with figures ranging from a negative $56 million to a positive $122 million.

Reneuron Seeks FDA OK For Human Stem Cell Trials

2006-12-10T10:21:00.000-08:00

Stem cell specialist Reneuron (RENE.LN) said Wednesday it's seeking approval from the U.S. Food and Drugs Administration to start testing its stroke therapy, ReN001, on human patients.

The Surrey, U.K.-based company, which has a market capitalization of less than GBP15 million, wants to conduct the trials on 12 humans. Trials on paralyzed rats showed that they regained some movement after treatment.

The trials would involve the injection of stem cells - taken from an aborted foetus - directly into the patients' brains. The tests would be carried out the Medical Centre at the University of Pittsburgh, with the patients under local anasthetic.

The news, which has sparked much ethical debate, drove ReNeuron shares almost 30% higher in early trading on London's Alternative Investment Market, AIM. At 1002 GMT, they were up 31%, or 4.6 pence, at 19.50 pence.

Chief Executive Michael Hunt said the company has already had "extensive" talks with the regulator and is "pretty confident".

Hunt believes the company will be able to meet concerns they FDA may have over the therapy's safety.

He said his team had sourced all the tissue it needed from one foetus.

"We're open about what we do. Clearly, there's an ethical issue here - but we have no need to extract more tissue, it was done with full maternal consent and it's also important to look at the patient benefit angle."

The use of embrionic stem cells - immature cells that have yet to have a function - destroys the embryo, and research in this area has sparked fierce ethical and moral debate. A different type of stem cell, known as adult cells, can be sourced from umbilical cords and bone marrow.

Hunt said the company will be tapping the market for further cash in the coming year.

The U.K. is seen as a supportive environment in which to conduct stem cell research, and the sector has received considerable Government support.

The Australian Parliament Wednesday lifted its ban on cloning human embryos for stem cell research, despite opposition from the prime minister and other party leaders. However, the anti-stem cell research in the U.S. remains very vocal. In 2001, President George Bush vetoed the use of public funds for stem cell research.

Reneuron has had a bumpy ride on the stock exchange. Founded in 1997 by scientists at London's Kings College, the company initially listed in 2000, valued at around GBP60 million, only to be taken private in 2003 for GBP3.6 million. The group subsequently relisted in 2005 at 25 pence per share.

Drug-Related Suicidal Thoughts May Abate With Age

2006-12-10T10:18:00.000-08:00

The Food and Drug Administration said antidepressants appear to increase the risk of suicidal thinking in young adults but that in older adults the risk declines.

The FDA reviewed data from 372 clinical studies involving 11 antidepressants including GlaxoSmithKline PLC's Paxil, Pfizer Inc.'s Zoloft and Eli Lilly & Co.'s Prozac. The studies involved almost 100,000 patients.

The FDA requested the data from drug makers last year in the wake of evidence antidepressants increased suicidal thoughts and behavior in children and adolescents to see if the same risk carried through to adulthood. The drugs carry a "black box" warning about the increased risk in children and adolescents.

The FDA review of the data, which date back to 1985, suggested a "differential risk of antidepressant-induced suicidality across the age spectrum." The agency said in documents posted to its Web site the risk was greater at the younger end of the spectrum and that it declined with age with a likely "protective" effect in adults age 65 and older.

The FDA review was posted ahead of a Dec. 13 advisory committee meeting scheduled to discuss the data and whether updated drug labels are needed to discuss the finding on suicidal thinking in adults. An FDA spokeswoman said the agency planned to update the labels but will seek the panel's input before the labels are changed.

This year, GlaxoSmithKline released an analysis of studies that involved 8,958 patients on Paxil and 5,953 on placebo, or a fake pill. Among the findings was a small but statistically significant increase in suicidal thoughts among young adults patients diagnosed with a major depressive disorder. The company updated Paxil's label warning doctors about the possibility of an increase in suicidal behavior in young adults.

Sanofi Drug Helps Diabetic Sugar Levels

2006-12-06T13:31:00.000-08:00

Sanofi-Aventis SA's obesity drug Acomplia can improve blood-sugar levels and weight loss in diabetic patients, according to a study presented at the World Diabetes Congress in South Africa.

The findings from the clinical trial have shown newly diagnosed patients with type-two diabetes who weren't taking antidiabetic drugs had significantly improved blood-sugar levels and lost more weight with Acomplia, compared with a dummy pill over a period of six months. In addition, Acomplia -- also known as rimonabant -- helped raise good cholesterol and control triglycerides, compared with a placebo.

The trial, the second study demonstrating that Acomplia can improve blood-sugar levels in people with type-two diabetes, was carried out on 278 diabetic patients whose sugar levels weren't responding adequately using a controlled diet alone.

Acomplia, hailed as a potential multibillion-dollar "blockbuster" drug and sold in several European countries, is the first in a new class of drugs that help with weight loss by curtailing cravings. Because it also controls blood-sugar levels, it might also become a future breakthrough to treat diabetics.

Given its potential as a diabetes drug, Acomplia is undergoing a number of clinical trials across the diabetes spectrum, from prediabetes patients to people who have to rely on daily insulin injections.

Acomplia's benefits shown in the trial support its use as a diabetes drug that is completely different from antidiabetic pills now on the market, said Julio Rosenstock, director of the Dallas Diabetes and Endocrine Center, an investigator in the trial.

Among the side effects reported by patients taking Acomplia were nausea, depressed mood and skin tingling, which led to a discontinuation rate of 9.4%, compared with 2.1% in the placebo patients.

"While Sanofi claims Acomplia is an important treatment for diabetes, the data have to be tempered with the side-effect issues," said Navid Malik, an analyst with London-based brokerage Collins Stewart.

In the trial, more than 50% of patients taking Acomplia achieved blood-sugar levels below 7%, the target for good glucose control, as recommended by the American Diabetes Association.

In addition, these improvements were linked to a weight loss of 14.7 pounds, compared with 5.9 pounds in patients on placebo.

Around 5% of adults world-wide have been diagnosed with diabetes, with type-two constituting the majority of diabetes cases in developed countries.

Glaxo Avandia Can Slow Diabetes Progression

2006-12-05T13:32:00.000-08:00

Long-term treatment with GlaxoSmithKline PLC's (GSK) blockbuster drug Avandia is more effective in slowing the progression of early-stage diabetes than two older treatments, according to a study published Monday in the New England Journal of Medicine.

The trial, presented Monday at the World Diabetes Congress in Cape Town, South Africa, showed that initial treatment of type-2 diabetes with Avandia slowed disease progression more effectively than did metformin and glyburide, which are currently used as first-line treatments.

Avandia is GlaxoSmithKline's second best-selling drug, with sales of GBP1.3 billion last year. It is prescribed to patients who do not respond to treatment with older anti-diabetics.

Compared with metformin, Avandia showed a risk reduction of 32%. This increased to 63% when it was compared with glyburide. The minimum target required in the trial, which studied 4,360 newly diagnosed diabetes patients over the course of four years, was a risk reduction of 30%.

However an accompanying editorial in the journal said that given Avandia's modest benefits, higher cost and side-effects, metformin remains "the logical choice" in the initial treatment of diabetes.

With all three drugs there was a high rate of patients dropping out of the trials due to adverse events. Around 60% of patients completed the study, the researchers said.

Treatment with Avandia highlighted a number of side-effects that are usually linked to the use of the drug, such as weight gain, increased levels of bad cholesterol and fluid retention.

However, Lawson Macartney, head of GlaxoSmithKline's cardiovascular and metabolic medicine development center, told an agency that the data underscore the fact Avandia performs significantly better than older drugs.

"Metformin performed well, but Avandia performed better," he said, noting that the data also support the effectiveness of combination therapy with both drugs in earlier-stage diabetes.

The trial showed that Avandia had clearer beneficial effect on older people and on those with a larger waist circumference.

Type-2 diabetes, the most common form of diabetes, is a chronic disease marked by high levels of sugar in the blood, and is more prevalent among older, overweight people. In addition to Avandia, GlaxoSmithKline's diabetes portfolio includes Avandamet, which is a combination of Avandia and metformin, as well as Avandaryl, which combines Avandia with glimepiride, an older oral antidiabetic.

GlaxoSmithKline is planning to file the results of the trial with drug regulators worldwide in the first half of 2007, Macartney said.

Bayer,Onyx:Nexavar Trial Doesn't Meet Targets

2006-12-05T13:28:00.000-08:00

Bayer AG (BAY) and its U.S. partner Onyx Pharmaceuticals Inc. (ONXX) said Monday that cancer drug Nexavar didn't meet the companies' primary targets in a trial to treat skin cancer.

Recently, shares of Bayer were up 5 cents at $51.90. Shares of Onyx were down $5.20, or 29.7%, at $12.30.

Late-stage Phase III tests on the treatment of advanced melanoma showed no improvement when Nexavar was compared with drugs already used to treat this kind of cancer, the companies said.

The target set by the companies was to improve the progression-free survival rate of patients suffering from advanced melanoma.

"This trial does not change our commitment to, and belief in, Nexavar," said Hollings Renton, chairman, president, and chief executive of Onyx.

The drug is already approved and on the market to treat renal cancer in the U.S., Europe and other countries.

Late November, Bayer reported third-quarter sales of the drug of EUR37 million and said it expects full-year 2006 sales to be over EUR100 million.

The companies are also evaluating Nexavar for treatment of liver and non-small-cell lung cancer, and are conducting the last of three clinical trials.

Pfizer Halt Of Torcetrapib Seen A Heavy Blow

2006-12-05T13:20:00.000-08:00

Pfizer Inc. (PFE) halted development of a drug to boost good cholesterol that was the most important medicine in its pipeline, after more patients than expected died during a large clinical test.

The unanticipated excess of deaths, whose number was small but wasn't specified by the company, became known Saturday after a board of independent experts reviewed the latest data from a 15,000-patient test of the drug called torcetrapib.

Citing patient safety, Pfizer said in a statement that it is terminating all clinical tests of torcetrapib and its plans to bring the drug to market.

The failure of torcetrapib is a heavy blow to Pfizer, the world's largest drug maker by sales. The company had bet on torcetrapib to take the place of cholesterol-fighter Lipitor, the company's best-selling product with $12.19 billion in revenue last year. Lipitor could lose patent protection as soon as 2010.

Doctors and investors have been watching torcetrapib closely because it seemed able to profoundly raise the type of cholesterol - called HDL - that could help keep arteries clear.

But torcetrapib has been dogged by safety worries. The medicine showed a tendency to raise blood pressure as it also raised good cholesterol.

Still, the increase in deaths for the patients who received torcetrapib was a shock. "We were very surprised ," said Philip Barter, director of the Heart Research Institute in Australia and chairman of the committee overseeing the large study, in the Pfizer statement. "We believed that the study was coming along as expected," he said.

Dr. Steven Nissen, chairmain of cardiovascular medicines at the Cleveland Clinic, called the setback "terribly disappointing." Nissen is the leader of another clinical test of torcetrapib to see if the medicine reversed the plaques that clog arteries feeding the heart. He said that finding new drugs to raise HDL safely and effectively remains an important goal. "We still don't know if this is a problem specific to torcertrapib or this approach to raising HDL isn't going to work."

The test that detected the more serious problems was a 15,000-patient study that was supposed to continue until 2009 or early 2010. Half the patients received tocetrapib plus Lipitor. The other half got Lipitor alone. Pfizer said the study cast no doubt on the safety and effectiveness of Lipitor.

Some analysts thought that the blood pressure problems that were already known would doom torcetrapib. Other companies, including Merck & Co. (MRK) and Roche Holding AG (RHHBY), were working on alternatives to torcetrapib that don't appear to increase blood pressure.

Only last Thursday Pfizer management had affirmed confidence in torcetrapib at a meeting with analysts to review the company's pipeline. The company affirmed its plan to seek Food and Drug Administration approval of torcetrapib taken in combination with Lipitor in the second half of 2007.

During the meeting, Pfizer research president John LaMattina said, "We believe this is the most important new development in cardiovascular medicine in years."

FDA Weighs Celebrex Studies On Juvenile Arthritis

2006-12-05T13:07:00.000-08:00

Pfizer Inc. might have to conduct further studies on its pain reliever Celebrex before it is approved to treat rheumatoid arthritis in children, the Food and Drug Administration staff said.

Celebrex, which is approved to treat arthritis in adults, has faced safety concerns over an increased risk of heart attacks and strokes for those who take it.

The drug belongs to the same class of painkillers as Merck & Co.'s Vioxx. Merck pulled the drug from the market in 2004 after its studies showed Vioxx doubled the risk of heart attacks and strokes. Pfizer continued to sell Celebrex after it strengthened label warnings about its risks.

This year the New York drug maker requested FDA approval for Celebrex to treat juvenile rheumatoid arthritis in patients ages two years and older. The FDA is holding a meeting today with an outside panel of experts, who will be asked to weigh the risks and benefits of the drug for the treatment in children.

According to documents posted on the FDA's Web site, about 30,000 to 60,000 children in the U.S. suffer from the condition. In severe, uncontrolled cases, rheumatoid arthritis can cause permanent disability.

While there are other drugs approved to treat the condition in children, "for some patients these approved products may provide limited efficacy or intolerable side effects," the FDA said. Those drugs include aspirin, ibuprofen and naproxen to treat the pain.

On the safety of the drug, the staff said "a key consideration" in assessing the issue "is the evidence of increased risk of cardiovascular adverse events in adults." Heart risks to children who take Celebrex long term are unknown.

In a trial conducted with children, the most common adverse events of Celebrex were certain infections and infestations, and nervous-system disorders. Compared with naproxen, common adverse events with Celebrex were similar in type and frequency, the staff said.

Drug Pipelineline Series: Phase III, 27 Nov - 4 Dec, 2006

2006-12-05T12:58:00.000-08:00

Dynavax's HEPLISAV™ Hepatitis B Vaccine Shows Statistically Significant Results in Phase 3 Trial

Dynavax Technologies Corporation announced statistically significant results from the primary endpoint analysis of a Phase 3 trial comparing HEPLISAV, its hepatitis B virus (HBV) vaccine, to GlaxoSmithKline's Engerix-B® vaccine in a difficult-to-immunize population of older adults. The primary endpoint is seroprotection four weeks after the third immunization.

The data show that after three doses, HEPLISAV provided seroprotection to 100% of subjects versus 73.1% for Engerix-B (p < 0.0001). The greatest difference in seroprotection after three doses was seen in subjects 56 to 70 years of age where HEPLISAV provided 100% seroprotection and Engerix-B provided 56.1%. Data for the entire study population show that after two doses, HEPLISAV provided 98.5% seroprotection versus Engerix-B's 25%. Furthermore, HEPLISAV provided a level of immunity as measured by geometric mean concentrations of anti-HBsAg antibodies 18.5 times higher than Engerix-B four weeks after the third dose.
The Phase 3 trial enrolled more than 400 seronegative subjects, 40 to 70 years of age, at study sites in Singapore, Korea and the Philippines. One group of subjects received three doses of Dynavax's HBV vaccine; the other group received three doses of Engerix-B.

Drug Pipelineline Series: Phase II, 27 Nov - 4 Dec, 2006

2006-12-05T12:51:00.000-08:00

CHEMOCENTRYX PRESENTS DATA FROM CROHN'S DISEASE STUDY

ChemoCentryx has presented data from a Phase II study of the company's drug candidate Traficet-EN (CCX282-B), a first-in-class, orally active, anti-inflammatory agent that targets the chemokine receptor known as CCR9, at the 2006 Crohn's and Colitis Foundation of America's annual meeting. New data were presented from a trial in patients with moderate-to-severe Crohn's disease analyzing the effect of Traficet-EN on lowering pro-inflammatory cytokine and chemokine concentrations in the intestine.

BAYER PUBLISHES RESULTS OF ANTICOAGULANT STUDY

Bayer has announced that results of a Phase II trial of the novel oral anticoagulant rivaroxaban, a direct Factor Xa inhibitor, have been published in Circulation. In the trial, rivaroxaban demonstrated that it may have similar safety and efficacy to subcutaneous enoxaparin (the current standard), for the prevention of venous thromboembolism (VTE) in patients undergoing elective total hip replacement surgery.

The publication completes the Phase II program with rivaroxaban for the prevention of VTE after major orthopaedic surgery and contains the full data set from the once-daily dosing trial; results from twice-daily trials in hip and knee replacement surgery have already been published. These data taken together formed the basis of the decision to initiate the Phase III program with rivaroxaban for the prevention of VTE after orthopaedic surgery using a once-daily dosing regimen.

Cleveland BioLabs Initiates Phase II Hormone-Refractory Prostate Cancer Trial for Curaxin CBLC102

Cleveland BioLabs, Inc. announced the initiation of its Phase II efficacy study for Curaxin CBLC102 in advanced, hormone-refractory (androgen independent) prostate cancer at the Cleveland Clinic and Case Western Reserve University Hospital.
Curaxin CBLC102 is a safe, oral drug used in the past to treat malaria that demonstrates efficacy in vitro, in animal models, and in live tumors removed from patients. Initial test results indicate that CBLC102 can be effective against a number of malignancies, including hormone refractory prostate cancer, renal cell carcinoma (a highly fatal form of kidney cancer), and soft-tissue sarcoma. The FDA permitted Cleveland BioLabs to advance directly to Phase II studies, based on CBLC102's historic safety profile.

Sangamo BioSciences Initiates Phase 2 Clinical Trial of Novel Therapy for Diabetic Neuropathy

Sangamo BioSciences, Inc. announced that the company has initiated a multi-center Phase 2 clinical trial of SB-509 for diabetic neuropathy (DN). The clinical trial is a double-blind, placebo-controlled, repeat-dosing study designed to evaluate the clinical safety and clinical effects of repeat administration of SB-509 in diabetics with mild to moderate diabetic peripheral sensory motor neuropathy in the legs. SB-509 is an injectable formulation of plasmid DNA that encodes a zinc finger DNA-binding protein transcription factor (ZFP TF™), designed to upregulate the vascular endothelial growth factor A (VEGF-A) gene.

Phase II Data Shows Ovation's Novel Compound Clobazam to Be Well Tolerated in Patients With Catastrophic Epilepsy

Results from the first study in the United States designed to evaluate the safety and efficacy of clobazam as adjunctive therapy in patients with Lennox-Gastaut syndrome (LGS), one of the most severe forms of childhood epilepsy, demonstrated that clobazam is well tolerated. In the trial, clobazam was shown to be effective in significantly reducing drop (or atonic) seizures, the most debilitating of the LGS seizure types, which can result in severe trauma to the brain and body, by 85.3 percent compared to baseline (in the high dose group versus 12 percent in the low dose group; P=.0001). Adverse events leading to the discontinuation of clobazam were rare. Data were presented at the North American Regional Epilepsy Congress.
This phase II, multi-center, randomized, double-blind, dose-finding clinical trial was the first study conducted in the U.S. to evaluate the safety and efficacy of clobazam as adjuvant therapy in patients with LGS. Sixty-eight patients (ages 2 to 26 years) with LGS were randomized to two treatment groups with a low dose (target of 0.25 mg/kg/day) of clobazam or a high dose (target of 1.0 mg/kg/day) for a total treatment duration of up to 10 weeks.

EPIX Announces Full Results from Phase 2a Clinical Trial of EP-2104R Presented at RSNA Annual Meeting

EPIX Pharmaceuticals, Inc. announced the results from a Phase 2a clinical trial of EP-2104R, a novel fibrin-binding thrombus (clot) imaging agent, as presented during an oral presentation at the Radiological Society of North America (RSNA) Annual Meeting in Chicago, Illinois. The results of the Phase 2a trial found that EP-2104R was able to detect blood clots not previously seen on magnetic resonance imaging (MRI) and enhanced the images of clots previously seen on MRI. Blood clots are a major underlying cause of several diseases including deep vein thrombosis, pulmonary embolism, heart attack and stroke, and identifying a minimally invasive method for detecting clots would address a substantial medical need.

Drug Pipelineline Series: Phase I, 27 Nov - 4 Dec, 2006

2006-12-05T12:40:00.000-08:00

Ligand Announces Initiation of Clinical Trials for Thrombocytopenia Drug, LGD 4665

Ligand Pharmaceuticals Incorporated announced that the Company is initiating Phase I clinical trials of LGD 4665, an oral, small molecule drug that mimics the activity of thrombopoietin (TPO), a growth factor that promotes growth and production of blood platelets.

Thrombocytopenia or low platelet count is a common clinical finding associated with a diverse group of clinical disorders or conditions affecting platelet production and/or survival. Prevalent clinical disorders where platelet loss or dysfunction leads to significant morbidity include idiopathic thrombocytopenia purpura (ITP), myelodysplastic syndrome, liver dysfunction associated with hepatitis C viral and severe cirrhosis, chemotherapy-induced thrombocytopenia (CIT) as well as a number of other disorders. Current therapeutic options are mostly palliative, including steroids, immunosuppresants, splenectomy and, for the most severe thrombocytopenias, platelet transfusion.

ARROW'S HEPATITIS C TREATMENT ENTERS PHASE I STUDY

Arrow Therapeutics has begun a Phase I study of A-831, a small-molecule antiviral inhibitor of the hepatitis C virus. The study will evaluate the safety, tolerability and pharmacokinetics of single escalating doses of A-831 in healthy volunteers in the UK.

A-831 targets the NS5a protein, a novel mechanism of action, and is the first NS5a inhibitor to enter clinical trials. The drug showed good safety and pharmacokinetics in preclinical studies and excellent potency in the replicon assay. A-831 is the first compound from Arrow's broad approach to the NS5a target.
The current standard treatment for hepatitis C, pegylated interferon plus ribavirin, has a poor side effect profile and is only effective in around 50 percent of patients, according to Arrow. Patients often need multiple drugs in combination therapy to overcome drug resistance.
The company also plans to develop other drugs for hepatitis C, which will be licensed to other companies between the preclinical and Phase IIb stages.

SEATTLE GENETICS BEGINS TRIAL OF HODGKIN'S LYMPHOMA DRUG

Seattle Genetics has initiated a Phase I clinical trial of SGN-35 for patients with Hodgkin's lymphoma and other CD30-positive hematologic malignancies. SGN-35 is an antibody-drug conjugate (ADC) that utilizes Seattle Genetics' proprietary technology to empower antibodies by linking them to potent cell-killing drugs.
The single-agent, dose-escalation study is designed to evaluate the safety, pharmacokinetic profile and antitumor activity of SGN-35 in patients with relapsed or refractory CD30-positive hematologic malignancies, including Hodgkin's lymphoma. The trial is expected to enroll up to approximately 40 patients at multiple centers in the United States.

SGN-35 is an ADC composed of an anti-CD30 antibody joined by an enzyme-cleavable linker to a potent, synthetic drug payload, monomethyl auristatin E (MMAE), using Seattle Genetics' proprietary technology. The ADC is designed to be stable in the bloodstream but to release MMAE upon internalization into CD30-expressing tumor cells, resulting in a targeted cell-killing effect. Treatment with SGN-35 resulted in complete tumor regressions in preclinical models of Hodgkin's disease and anaplastic large-cell lymphoma.

Pain Therapeutics Announces Positive Phase I Study Results With PTI-202

Pain Therapeutics, Inc. announced positive results from a Phase I clinical trial evaluating PTI-202, the Company's second abuse- resistant opioid painkiller.
This clinical trial was designed to investigate the safety, tolerability, pharmacokinetics and pharmacodynamic profile of a single, oral dose of PTI-202 in healthy volunteers. We believe results also indicate PTI-202 is safe and well-tolerated and its release profile appears well-suited to use with a chronic pain population. There were no unexpected adverse events in this trial.
PTI-202 is a novel abuse-resistant formulation of an opioid painkiller. Its active pharmaceutical ingredient remains undisclosed. PTI-202 is intended to meet the needs of physicians who appropriately prescribe opioid painkillers and who seek to minimize the risks of drug diversion, abuse or accidental patient misuse.

Novartis Files Drugs For Approval Ahead Of Plan

2006-11-29T01:51:00.001-08:00

Swiss drugmaker Novartis AG (NVS) Tuesday said it has submitted a bone and a cancer drug for regulatory approval earlier than planned, and added that it is starting late-stage testing on five experimental medicines.

Demonstrating that it has one of the strongest pipeline of new drugs in the industry, Novartis, based in Basel, said it has a total of 138 projects in development, comprising both new possible treatments for disease for which there is no cure, as well as studies for possible new uses of medicines that are already on the market.

Around two thirds of these projects are in the second and third phase of clinical testing. Most drugs are being studied in three phases of testing before companies submit them for regulatory approval.

"Over the next two years we will launch several innovative medicines and continue to invest aggressively in discovery research and development activities and complement our own skills and technologies through attractive collaborations," chief executive Daniel Vasella said in a statement.

The Swiss drugmaker also suffered some setbacks, terminating the development of osteoporosis medicine AAE581 and of anxiety drug XBD173, while saying that the development of LIC477, a potential new treatment for manic-depression, was delayed. Analysts had expected Novartis to submit LIC477 for regulatory approval next year.

Development of cancer drug EPO906 is also progressing more slowly than planned because the company failed to recruit patients fast enough to the clinical testing phase.

In addition, experimental diabetes treatment Galvus, a potential blockbuster with expected annual sales of at least $1 billion, was shown to work less well than metformin in a two-year trial, confirming results already seen after one year of treatment.

Novartis expects the U.S. Food and Drug Administration to decide on approving this drug in the first half of 2007. Analysts generally expect Galvus to win approval, but that the drug, which treats diabetes in a new way, will come to the market about half a year later than Januvia, a similar drug, for which its maker Merck & Co. (MRK) gained U.S. approval recently.

In contrast, hypertension drug Tekturna, another potential blockbuster, was shown to lower blood pressure more effectively than a diuretic, or water pill. Diuretics are commonly prescribed hypertension treatments, and are available as cheap generics. Tekturna, which was developed jointly with Speedel Holding AG, a small Swiss pharmaceutical company, was also shown to work well in combination with Diovan, the company's best-selling drug.

"The data on the Tekturna-Diovan combination are very important, because they will essentially allow Novartis to double the life cycle of Diovan," said Karl-Heinz Koch, analyst in Zurich with private bank Vontobel, who has a buy rating on the stock. "As a result, rather than falling to around $2 billion as expected, hypertension sales will remain at around $6 billion after the patent expiration of Diovan."

Diovan, which had sales of $3.68 billion in 2005, will lose patent protection in 2012.

Having accelerated the submissions for regulatory approval in Europe and the U.S., Novartis has filed for approval of cancer drug Tasigna, and bone drug Aclasta. Many analysts had expected the filing of these drugs only later in 2006 or next year.

Tasigna, or nilotinib, was filed for approval for use in patients with resistance or intolerance to treatment with Gleevec for certain forms of chronic myeloid leukemia. Gleevec is also a Novartis drug and the company's second-best selling product after hypertension drug Diovan. A few months ago, Bristol-Myers Squibb Co. (BMY) received U.S. approval for Sprycel, a drug that some analysts consider a potential threat to Gleevec sales. Sprycel was approved for use in patients for whom Gleevec doesn't work.

The second drug, Aclasta, or zoledronic acid, is a once a year infusion for the treatment of women with postmenopausal osteoporosis. The most frequently prescribed osteoporosis drugs available today need to be taken once a week, which is a drawback that leads to poor compliance among patients, because the drugs are cumbersome to take.

In its first detailed update on drugs in development in almost two years, Novartis also said that five experimental drugs are moving into the third, and usually last, phase of clinical testing.

They are: FTY720, or fingolimod, for multiple sclerosis, QAB149, or indacaterol for smoker's cough and asthma, AG0178, or agomelatine, for depression and ABF656, or albuferon for hepatitis C, as well as RAD001, or everolimus, for cancer and SOM230, asireotide, for Cushing's disease.

Akzo, Pfizer End Collaboration On Asenapine

2006-11-29T01:51:00.000-08:00

Dutch chemical group Akzo Nobel NV (AKZOY) and U.S. drug maker Pfizer (PFE) Tuesday said they will end joint development of a drug seen as a key factor in the planned stock market listing of Akzo's pharmaceuticals unit.

Asenapine, a new drug candidate for treating schizophrenia and acute mania associated with Bipolar I Disorder, had been expected to become the first billion-dollar blockbuster drug for the Organon BioSciences unit.

But Pfizer - the world's leading drugmaker measured by prescription sales - said "commercial considerations" had caused it to withdraw.

Akzo said it remains fully committed to bringing the new drug to market, and stressed the move will not derail plans to float Organon in early 2007.

Analysts said Pfizer's decision to withdraw was negative for Akzo Nobel and cast doubt over the flotation. Analysts said the success of the new drug remains uncertain, and that without Pfizer, the product's sales potential looks shaky.

"That Pfizer (PFE) is abandoning the partnership deal with Akzo Nobel (AKZOY) on the development of the new drug asenapine is bad news for Akzo Nobel," said Rabo Securities-analyst Mark van der Geest, who rates Akzo Nobel hold.

Akzo Nobel shares at 1102 GMT were down 0.5%, or EUR0.2 lower, at EUR41.84 in a firmer overall market.

Toon Wilderbeek, Organon BioSciences chief executive officer said Organon's plans for an initial public offering remain on course. "This will not affect the IPO - We are still planning to list a minority of the shares on Euronext Amsterdam."

Akzo Nobel aims to list 20% to 30% of Organon so that the group can concentrate on its profitable coatings and chemicals sectors.

Akzo Nobel now must decide whether it needs another partner to commercialize asenapine, Wilderbeek said in a statement. Pfizer said it will return all product rights, intellectual property and data on Asenapine to Organon during 2007.

Under terms of their 2003 co-development pact, Pfizer paid Akzo Nobel $100 million up front in initial fees and was committed to pay up to $270 million in milestone payments if asenapine received regulatory approval in the U.S., Europe and Japan and reached certain sales targets.

Analyst Danny van Doesburg of SNS Securities said that the fact that Akzo Nobel will now develop the drug on its own is bad news because now it will have to pay all costs related to the development of Asenapine.

"If the drug makes it to the market, and the drug starts bringing in revenues, Akzo Nobel will have to pay a total of $350 million to Pfizer," he said.

He said one positive aspect is however that Akzo will consequently not have to share revenues with Pfizer once the drug is on the market. Van Doesburg rates Akzo a hold and has a price target of EUR48.

Akzo Nobel said Organon will now assess whether further clinical trials are needed to convince the U.S. Food and Drug Administration that asenapine is a useful drug. In October phase II trials for asenapine weren't sufficiently conclusive for Akzo Nobel to seek approval for filing the drug to the US Food and Drug Administration.

Drug Pipeline Series: Submissions, Nov 20 - Nov 27, 2006

2006-11-28T13:04:00.000-08:00

Anesiva Announces Filing of New Drug Application for Zingo™ to Reduce Pain Associated with Needle Insertion Procedures in Children
Anesiva, Inc. announced that the company has filed a New Drug Application (NDA) with the FDA for marketing clearance of Zingo™ to treat the pain associated with venous access procedures in children. As part of the company's continued development of Zingo, Anesiva expects to begin a follow-on clinical trial in adults in early 2007. As previously announced, Anesiva has obtained commitments to purchase approximately $45 million of its common stock, which it anticipates closing on November 28, 2006.

Drug Pipeline Series: Phase III, Nov 20 - Nov 27, 2006

2006-11-28T13:00:00.000-08:00

Dyax Announces Final Patient Treated in Pivotal Phase III Clinical Trial (EDEMA3) for DX-88 in Hereditary Angioedema
Dyax Corp. announced that it has completed the double-blind portion of its pivotal Phase III clinical trial, known as EDEMA3, for its lead product candidate DX-88 (ecallantide) for the treatment of hereditary angioedema (HAE). In addition, the U.S. Food and Drug Administration has also broadened the Fast Track designation for DX-88 for the treatment of all types of acute HAE attacks, a rare and life-threatening inflammatory condition for which there is no approved therapy in the United States.

First Patient Treated in Phase III Ovarian Cancer Trial
Marshall Edwards, Inc. announced that the first patient had commenced treatment in the Phase III "OVATURE" clinical trial at The Royal Women's Hospital in Melbourne, Australia.
Royal Women's is one of 60 hospitals that will be participating in this multi-center multi-national ovarian cancer study to confirm the effectiveness of phenoxodiol in resensitizing patients to chemotherapy.

SOMAXON REPORTS RESULTS FROM THIRD PHASE III STUDY OF SILENOR
Somaxon Pharmaceuticals has announced positive results from its Phase III clinical trial evaluating Silenor (doxepin HCl) in elderly patients with primary sleep maintenance insomnia. The drug demonstrated a statistically significant improvement compared with placebo in the primary endpoint of this trial, subjective total sleep time as measured at week one. Statistical significance was maintained for all time points measured throughout the four-week treatment period.

Drug Pipeline Series: Phase II, Nov 20 - Nov 27, 2006

2006-11-28T12:57:00.000-08:00

Genzyme Begins Phase 2 Pivotal Study of Clolar® in Adult Acute Myelogenous Leukemia
Genzyme Corporation announced that it has begun treating patients in a phase 2 clinical trial examining the safety and effectiveness of Clolar® (clofarabine) in previously untreated, older adult patients with acute myelogenous leukemia (AML) who are unlikely to benefit from standard induction therapy.
This is Genzyme's second pivotal clinical study of clofarabine in adult patients with AML to commence this year, and it is expected to provide substantial support for expanding the current product label.

BIOMS MEDICAL BEGINS TRIAL OF TREATMENT FOR MS
BioMS Medical has announced that the first patients have been enrolled in its placebo-controlled, multicenter, Phase II clinical trial of MBP8298 for the treatment of relapsing-remitting multiple sclerosis (RRMS).
The 15-month, double-blind, placebo-controlled trial will enroll up to 215 patients with RRMS from up to 30 sites. The trial will be followed by a 12-month open-label extension period. The objectives of the study are to demonstrate safety and efficacy of MBP8298 versus placebo as measured by relapse rate, MRI activity and disease progression.
MBP8298 is also currently undergoing a pivotal Phase III trial for the treatment of secondary progressive multiple sclerosis (SPMS) patients with immune response genes HLA-DR2 and/or DR4.

Drug Pipeline Series: Phase I, Nov 20 - Nov 27, 2006

2006-11-28T12:28:00.000-08:00

FIBROGEN ANNOUNCES DATA ON CTGF ANTIBODY IN MICROALBUMINURIA
FibroGen has announced results of a Phase Ib study of FG-3019, a fully human monoclonal antibody against connective tissue growth factor (CTGF), in people with Type 1 or 2 diabetes and microalbuminuria, the earliest clinical sign of diabetic nephropathy.
The primary objectives of this open-label, multiple-dose, sequential-group, dose-escalation, multicenter study were to characterize the safety, tolerability and pharmacokinetics of FG-3019. Results demonstrated that FG-3019 was well-tolerated. Only one serious adverse event was reported, which was considered unrelated to the study drug. No dose-limiting toxicities were observed. Clearance of FG-3019 was saturable, and accumulation of FG-3019 in the bloodstream was limited during the dosing interval.

AEterna Zentaris Reports Positive Top Line Phase 1 Results for AN-152 in Patients with Gynaecological and Breast Cancers
AEterna Zentaris Inc. disclosed additional positive top line Phase 1 results for its cytotoxic conjugate AN-152 in patients with gynaecological and breast cancers. Further data showed the compound's good safety profile and established the maximum tolerated dose (MTD) at 267 mg/m(2) which will be the recommended dose for a Phase 2 trial. In addition to good safety data, the trial provided a hint of efficacy as disease stabilization and regression of lesions were observed at the 160 mg/m(2) and 267 mg/m(2) dose levels.

PEREGRINE BEGINS COMBINATION THERAPY CANCER TRIAL
Peregrine Pharmaceuticals has initiated a Phase Ib clinical trial to evaluate its lead anti-phospholipid immunotherapy agent bavituximab given in combination with common cancer chemotherapy agents. The trial is expected to enroll up to 12 patients at three clinical sites in India.
The trial is designed to test the safety and tolerability of bavituximab over an eight-week administration period when given with standard chemotherapy regimens including docetaxel, gemcitabine and carboplatin/paclitaxel. These regimens are commonly used for treating major cancer types, including breast, lung and pancreatic cancer. Study endpoints include safety and drug pharmacokinetics. Patients will also be evaluated for tumor response according to Response Evaluation Criteria in Solid Tumors criteria, although this assessment is not a formal endpoint of the study. Patients will be followed for an additional four weeks after their last dose of bavituximab and may continue with chemotherapy according to standard-of-care guidelines.

NEOPHARM PRESENTS SAFETY DATA ON MALIGNANT GLIOMA TREATMENT
Neopharm has announced the presentation of final Phase I safety results at the Society for Neuro-Oncology's annual meeting. Data from this 22-patient trial showed that 0.5 micrograms/mL of Cintredekin Besudotox delivered via convection-enhanced delivery followed by external beam radiation therapy (EBRT), with or without concurrent temozolomide, following tumor resection appears to be safe in patients with newly diagnosed malignant glioma.

Kamada Begins Phase I Clinical Trials of Its Aerosolized API Treatment for Congenital Emphysema
Kamada announced that it has begun human Phase I trials of an inhaled formulation of its flagship drug, Alpha 1-Proteinase Inhibitor (API). The trials will examine the product's safety on approximately 20 participants and will continue for several months according to a plan approved by the EMEA, the European Agency for Evaluation of Medicinal Products.

Drug Pipeline Series: Approvals, Nov 13 - Nov 20, 2006

2006-11-23T04:14:00.000-08:00

FDA Approves Herceptin® for the Adjuvant Treatment of HER2-Positive Node-Positive Breast Cancer
Genentech, Inc. announced that the U.S. Food and Drug Administration (FDA) approved Herceptin® (Trastuzumab), as part of a treatment regimen containing doxorubicin, cyclophosphamide, and paclitaxel, for the adjuvant treatment of HER2-positive node-positive breast cancer. Adjuvant therapy is given to women with early-stage (localized) breast cancer who have had initial treatment - surgery with or without radiation therapy - with the goal of reducing the risk of cancer recurrence and/or the occurrence of metastatic disease.
The FDA approval was based on data from an interim joint analysis of more than 3,500 patients enrolled in two Phase III clinical trials. These results showed that the addition of Herceptin to standard adjuvant therapy significantly reduced the risk of breast cancer recurrence, the primary endpoint of the studies, by 52 percent (or a hazard ratio of 0.48) in women with HER2-positive breast cancer, compared to those patients who received standard adjuvant therapy alone.

Abbott's HUMIRA® (adalimumab) Receives FDA Approval for Inhibiting Structural Joint Damage and Improving Physical Function in Patients With Psoriatic Arthritis
Abbott announced that the U.S. Food and Drug Administration (FDA) approved an expanded indication for HUMIRA® (adalimumab) that includes inhibiting structural joint damage and improving physical function in patients with psoriatic arthritis (PsA). The expanded indication is in addition to the psoriatic arthritis approval granted in October 2005.
HUMIRA is also approved in the U.S. for use in moderate to severe rheumatoid arthritis (RA) and active ankylosing spondylitis (AS).
The expanded indication is based on results from an extension of the Adalimumab Effectiveness in Psoriatic Arthritis Trial (ADEPT), the largest randomized, placebo-controlled biologic trial in PsA. ADEPT was a Phase III, controlled study in 313 patients with moderate to severe PsA, who had an inadequate response to NSAID (non-steroidal anti-inflammatory drug) therapy. Patients were randomized to receive either HUMIRA 40 mg every other week or placebo. At week 24, 285 patients elected to enroll in a 24-week open-label extension.

Allergan Announces FDA Approval of INAMED® Silicone-Filled Breast Implants for Breast Augmentation, Reconstruction and Revision Surgery
Allergan, Inc. announced that the United States Food and Drug Administration (FDA) has approved Allergan's INAMED® Silicone-Filled Breast Implants for use in breast augmentation, reconstruction and revision surgery. Until , INAMED® Silicone-Filled Breast Implants were only available in the United States to women seeking breast reconstruction and revision surgery through clinical studies. The approval is a significant development for women in the United States who now have the same options that women in more than 60 countries have had for the last 25 years.
Silicone gel-filled breast implants are among the most studied medical devices in existence, with thousands of peer-reviewed and published reports on studies, including robust epidemiological studies supporting their safe use. The safety of INAMED® Silicone-Filled Breast Implants is supported by the company's extensive pre-clinical device testing, their use in approximately 1,000,000 women worldwide and nearly a decade of U.S. clinical experience involving more than 80,000 women. Furthermore, silicone is used safely in the body in many medical devices and products, including pacemakers, heart valves, artificial joints and baby pacifiers.

Drug Pipeline Series: Submissions, Nov 13 - Nov 20, 2006

2006-11-23T04:13:00.000-08:00

Angiotech submits application for European regulatory approval for its Vascular Wrap™ product
Angiotech Pharmaceuticals, Inc. announced that it has submitted an application for a CE Mark for its Vascular Wrap™ paclitaxel-eluting mesh / ePTFE vascular graft combination product on the strength of the results from its European first-in-man study.
The two-year trial which supports the CE Mark application produced evidence that treatment with the Vascular Wrap reduced the overall incidence of leg amputation and prolonged limb retention time in patients suffering from late stage peripheral arterial disease who underwent bypass surgery. For the patients that required an amputation during the study period, the mean interval to amputation for patients treated with the Vascular Wrap was 156 days - more than double the mean interval to amputation for the control, which was 76 days. At the same time, the Vascular Wrap appeared to be well tolerated, with no adverse events being considered related to the use of the product.

About peripheral arterial disease
Angiotech's Vascular Wrap™ paclitaxel-eluting mesh / ePTFE graft combination product technology is being developed for use in hemodialysis access and peripheral arterial bypass surgery. It is a combination product consisting of both the ePTFE graft and the Vascular Wrap paclitaxel-eluting mesh. The Vascular Wrap component is a biodegradable mesh implant incorporating Angiotech's paclitaxel technology in a novel biomaterial with the goal of mitigating scar formation caused by abnormal blood flow thereby potentially enhancing graft patency rates in AV-access patients as well as in peripheral bypass procedures.

Drug Pipeline Series: Phase III, Nov 13 - Nov 20, 2006

2006-11-23T04:10:00.000-08:00

DVANCED MAGNETICS REPORTS POSITIVE RESULTS FROM IRON-REPLACEMENT STUDY
Advanced Magnetics presented positive results from a Phase III clinical trial of ferumoxytol as an intravenous iron replacement therapeutic at the American Society of Nephrology's annual meeting.
The study enrolled 304 non-dialysis-dependent chronic kidney disease patients who were randomized to receive either two 510-mg doses of ferumoxytol within one week or 200 mg of oral iron daily for three weeks. The study demonstrated a statistically significant achievement of all the primary and secondary endpoints. Additionally, all endpoints were statistically significant in both patients on erythropoiesis stimulating proteins (ESP) and those not on ESPs.
Efficacy results in the intent-to-treat and efficacy-evaluable populations were similar. In the intent-to-treat population, ferumoxytol significantly outperformed oral iron for the primary endpoint of change in hemoglobin at day 35.
The results from the efficacy-evaluable population analysis showed that at day 35 patients receiving ferumoxytol had a significantly greater mean increase in hemoglobin compared with patients in the oral iron group. Ferumoxytol was more likely to increase baseline hemoglobin by greater than or equal to 1 g/dL compared with oral iron. Also, an increase in serum ferritin was significantly greater in the ferumoxytol group compared with the oral iron group at day 21. Stratifying by ESP use, there was a significant difference in hemoglobin increase for ferumoxytol compared with oral iron in both patients who were on ESP and those who were not.
Ferumoxytol was well-tolerated with repeated dosing. Adverse events occurred in 52.0 percent of oral iron patients compared with 35.5 percent of ferumoxytol patients. Similarly, drug-related adverse events occurred in 24.0 percent of oral iron patients compared to 10.6 percent of ferumoxytol patients.

Medicure Announces Initiation Of Enrollment In Pivotal Phase III MEND-CABG II Study
Medicure Inc. announced it has commenced enrollment in the MEND-CABG II study. This single confirmatory Phase III study for registration will evaluate the cardioprotective effects of the Company's FDA Fast Tracked product, MC-1, in approximately 3,000 patients undergoing coronary artery bypass graft (CABG) surgery.
MEND-CABG II is a double-blind, randomized, placebo-controlled clinical trial that will enroll up to 3,000 patients undergoing CABG surgery at approximately 120 cardiac surgical centers throughout North America and Europe. The study design was reviewed with the United States Food and Drug Administration (FDA). Study patients will be randomized to receive placebo or MC-1 250mg prior to surgery and for 30 days post operatively (POD 30). The primary efficacy endpoint of MEND-CABG II is the reduction in the composite of cardiovascular death and non-fatal myocardial infarction up to POD 30. Study patients will be followed for 60 days after treatment (90 days post operatively) for additional safety and efficacy analysis.

Auxilium Pharmaceuticals, Inc. Initiates Phase III Trials for AA4500 in Dupuytren's Contracture
Auxilium Pharmaceuticals, Inc. announced that the first patients have been dosed in the Company's second U.S. Phase III pivotal trial and the first Phase III study outside the U.S. for AA4500 for the treatment of Dupuytren's contracture, a disabling and recurring condition in which the joints in the hand contract, impairing patients' ability to straighten and move their fingers.
The U.S. study is a double-blind, randomized, placebo controlled study of AA4500 involving more than 200 patients at up to 15 sites throughout the U.S. Patients in the study will be randomized on a 2:1 basis in favor of AA4500 treatment. To qualify for the study, patients must have at least 20 degrees of contracture. The primary endpoint of the study is to determine if AA4500 can reduce the contracture angle to within 0 to 5 degrees of normal as measured by digital goniometry.

Vanda Pharmaceuticals' VEC-162 Demonstrates Positive Results in a Phase III Transient Insomnia Clinical Trial
Vanda Pharmaceuticals Inc. announced positive top-line results from the company's Phase III clinical trial evaluating VEC-162, a balanced melatonin receptor agonist, in transient insomnia. VEC-162 demonstrated statistically significant improvements at all three tested doses compared to placebo (p<0.001) in the primary endpoint of the trial, Latency to Persistent Sleep (LPS), a measure of sleep onset. VEC-162 also produced statistically significant improvements relative to placebo in Latency to Non-Awake (LNA), another measure of sleep onset, Wake After Sleep Onset (WASO), a measure of sleep maintenance, and Total Sleep Time (TST). VEC-162 was also demonstrated to be safe and well-tolerated.
The Phase III trial was a randomized, double-blind, placebo-controlled, multi-center study that enrolled 412 adults in a sleep laboratory setting using a phase-advance, first-night assessment model of induced transient insomnia. The trial examined VEC-162 dosed 30 minutes before bedtime at 20, 50 and 100 mg versus placebo.

MEDICINOVA BEGINS TRIAL PROGRAM FOR ASTHMA TREATMENT
MediciNova has initiated a Phase III clinical program to determine the safety and efficacy of its novel oral treatment for bronchial asthma, MN-001.
The first Phase III trial in this program will involve approximately 705 asthma patients enrolled at 75 to 90 clinical sites in the U.S. Mild-to-moderate asthma patients will receive placebo or MN-001 for 12 weeks in this randomized, placebo-controlled, double-blind study. The primary endpoint of the trial will be the change from baseline in mean FEV1 (forced expiratory volume in one second) after 12 weeks of treatment. Secondary outcome measures will include a self-administered asthma quality-of-life questionnaire, the change from baseline in morning and evening peak flow rates, rescue beta-agonist use, serial spirometry parameters including assessment of acute effects following first dose on day one, daytime asthma symptom scores, nighttime awakenings from asthma, physician's global assessment, number of asthma exacerbations, discontinuations due to asthma, clinical global impression evaluations and change in urinary LTE4 levels. Additional Phase III trials are planned. Development of a continuous-release formulation of MN-001 will parallel the initial Phase III trials.
MN-001 is a novel, orally bioavailable compound that has been shown to block a number of the inflammatory mechanisms activated by mast-cell degranulation (e.g., leukotriene receptor antagonism and inhibition of phosphodiesterases III and IV, 5-lipoxygenase, phospholipase C and thromboxane A2) that are important in the pathogenesis of inflammatory disorders including asthma.
MN-001 is also under development by MediciNova for the treatment of interstitial cystitis. MN-001 is currently being evaluated in a pivotal-design Phase II/III clinical trial in 305 patients with moderate-to-severe interstitial cystitis at 39 clinical sites in the U.S. MediciNova anticipates having results from this trial by the beginning of 2007.

Drug Pipeline Series: Phase II, Nov 13 - Nov 20, 2006

2006-11-22T00:57:00.000-08:00

CuraGen and TopoTarget Announce Initiation of NCI-sponsored Phase II Clinical Trial of PXD101 for Myelodysplastic Syndrome
CuraGen Corporation and TopoTarget A/S announced the initiation of patient dosing in a Phase II open-label, multi-center clinical trial evaluating the efficacy and safety of intravenous PXD101, a small molecule histone deacetylase (HDAC) inhibitor, for the treatment of Myelodysplastic Syndromes (MDS). This trial is being sponsored by the National Cancer Institute (NCI) under a Clinical Trials Agreement with CuraGen for PXD101.
The primary endpoint for the study is the proportion of confirmed responses as defined by the International Working Group. Secondary endpoints include the time to progression, overall survival, duration of response, and toxicity. The pharmacodynamic activity of PXD101 will also be evaluated by the assessment of histone acetylation, gene expression profiling and DNA methylation. Patients will be enrolled at multiple sites in the United States.

Helix Biopharma Completes Phase 2 Clinical Study With Topical Interferon Alpha-2B In Patients With Low-grade Squamous Intraepithelial Lesions
Helix BioPharma Corp. announced completion of enrollment and treatment in its Phase 2 clinical study of Topical Interferon Alpha-2b in women with low-grade squamous intraepithelial lesions ("LSIL") that are positive for human papilloma virus ("HPV") infection.
The study was designed to evaluate the safety and effectiveness of Topical Interferon Alpha-2b in patients with cytologically confirmed LSIL and polymerase chain reaction ("PCR") confirmed HPV. Patients received Topical Interferon Alpha-2b therapy applied intravaginally three times a week for a period of six weeks, followed by a six week follow-up period. The primary study endpoint is to determine the proportion of patients with resolution of their abnormal Pap smear during the twelve week study duration.
No serious adverse drug reactions were reported in the study. The Company is completing analytical work on patient samples collected over the duration of the patient testing and will be gathering and analyzing the final data. The Company expects to complete all data analyses and report the final integrated study findings during the first quarter of calendar 2007.

Human Genome Sciences Announces Positive 76-Week Results of Phase 2 Clinical Trial of LymphoStat-B™ in Systemic Lupus Erythematosus
Human Genome Sciences, Inc. announced that the 76-week results of a Phase 2 clinical trial demonstrated that LymphoStat-B™ (belimumab) reduced disease activity in patients with serologically active systemic lupus erythematosus (SLE), exhibited durable biological activity, and appeared safe and well tolerated. In the LymphoStat-B treatment groups, the percentage of serologically active SLE patients who achieved the combined response rate selected as the primary efficacy endpoint for Phase 3 trials of LymphoStat- B™ increased from 46% at Week 52 to 56% at Week 76, with no increase in infections or infectious events observed over time.
The results were presented in two oral presentations in Washington, DC at the 70th Annual Meeting of the American College of Rheumatology/ Association of Rheumatology Health Professionals (ACR/ARHP). Additional LymphoStat-B results were reported in poster presentations throughout the meeting.

Quigley Pharma's QR-333 Phase IIb Clinical Study Has Commenced; Drug Product and Clinical Trial Sites Prepared for Phase IIb Study of Lead Drug Candidate
Quigley Pharma Inc. announced that patient enrollment in a phase IIb multi center clinical study of QR-333 for the treatment of symptomatic Diabetic Peripheral Neuropathy (DPN) has commenced. The Phase IIb double blind multi-center study will evaluate the safety and efficacy of QR-333, as compared to placebo-treated patients. The active QR-333 Investigational New Drug and placebo have been prepared for shipment and will be available to clinical investigators to begin treatment starting in December.
The Phase IIb trial will evaluate the safety and efficacy of QR-333 applied three times daily compared to placebo-treated patients over 12 weeks. Efficacy will be determined by Symptom Assessment Scores, a Visual Analogy Scale (VAS), Quality of Life and Sleep Questionnaires. Safety will be determined by medical history, physical examination, vital signs, 12-lead ECG, laboratory tests and nerve conduction studies. The study will involve 150-200 randomized male and female patients with Type 1 & 2 diabetes, as defined by the ADA (American Diabetes Association) and distal symmetric diabetic polyneuropathy.

EVOTEC BEGINS TRIAL OF INSOMNIA DRUG IN ELDERLY PATIENTS
Evotec has announced the initiation of a second Phase II study with EVT 201 under an investigational new drug application. This randomized, multicenter, double-blind study is a parallel design study with two doses of EVT 201 and placebo in 135 elderly patients with chronic primary insomnia and daytime sleepiness. It is designed to assess the hypnotic efficacy of EVT 201 during seven nights of treatment and also to determine the effect of improved sleep quality on daytime performance.
According to the company, the elderly are a significant portion of the insomnia patient population.
The primary endpoint of this trial is to assess total sleep time determined by polysomnography. The secondary endpoints include a variety of tests of daytime sleepiness and functional performance as well as additional sleep efficacy measures such as latency to persistent sleep, wake after sleep onset and number of awakenings, determined by polysomnography. In addition, effects on sleep architecture will be examined and patients will evaluate sleep quality and quantity subjectively.
In September Evotec initiated its first Phase II clinical trial with EVT 201, which is ongoing. Prior to this, in two Phase I/II studies using the traffic noise model of insomnia in healthy male volunteers, EVT 201 significantly reduced wake after sleep onset while significantly increasing total sleep time and quality of sleep with no subjective residual effects. The compound was well-tolerated without significant adverse events.

Drug Pipeline Series: Phase I, Nov 13 - Nov 20, 2006

2006-11-22T00:53:00.000-08:00

SURFACE LOGIX PRESENTS POSITIVE DATA ON DYSLIPIDEMIA DRUG
Surface Logix announced the presentation of positive data from its first Phase I clinical trial assessing the safety and tolerability and establishing the pharmacokinetic and pharmacodynamic profile of its investigational drug candidate for dyslipidemia, SLx-4090. Results were presented at the American Heart Association's conference in Chicago.
SLx-4090 is a novel microsomal triglyceride transfer protein (MTP) inhibitor being developed for the treatment of dyslipidemia. Surface Logix designed SLx-4090 using its proprietary small-molecule Pharmacomer Technology to act specifically in the gastrointestinal (GI) tract to prevent the transport of fats through the intestinal wall. This unique feature of intestinal selectivity allows activity against fat uptake while avoiding toxicity at other sites of MTP expression including the liver, heart, testis, ovary and eye, according to the company.

SOSEI BEGINS TRIAL OF EMERGENCY CONTRACEPTIVE PILL
Sosei has announced the initiation of a Phase I clinical trial for the emergency contraceptive pill NorLevo. Sosei acquired the exclusive distribution rights to the product in Japan from Laboratoire HRA Pharma, and it is currently approved and marketed in more than 50 countries.
NorLevo is an oral emergency contraceptive used to prevent pregnancy after unprotected intercourse. NorLevo contains only levonorgestrel as an active ingredient. The dosing is started within 72 hours after unprotected sexual intercourse.
As a result of a large multinational study in 1998, the World Health Organization (WHO) demonstrated that levonorgestrel monotherapy, such as NorLevo, was well-tolerated and more effective than the Yuzpe method (ethinyl estradiol and levonorgestrel), an emergency contraception method used since 1977. Levonorgestrel monotherapy for emergency contraception is listed by WHO as an essential drug, according to Sosei.

Seattle Genetics Initiates Phase I Clinical Trial of SGN-35
Seattle Genetics, Inc. announced that it has initiated a phase I clinical trial of SGN-35 for patients with Hodgkin's disease and other CD30-positive hematologic malignancies. SGN-35 is an antibody-drug conjugate (ADC) that utilizes Seattle Genetics' proprietary technology to empower antibodies by linking them to potent cell-killing drugs.
The single-agent, dose-escalation phase I study is designed to evaluate the safety, pharmacokinetic profile and antitumor activity of SGN-35 in patients with relapsed or refractory CD30-positive hematologic malignancies, including Hodgkin's disease. The trial is expected to enroll up to approximately 40 patients at multiple centers in the United States.

Probe: Cephalon Used Improper Tactics To Sell Drug

2006-11-21T12:32:00.000-08:00

From setting unrealistically high sales quotas to pushing larger prescriptions at higher doses, drug maker Cephalon Inc. engaged in questionable practices to expand sales of Actiq, a powerful narcotic lollipop approved only to treat cancer pain, according to a two-year investigation by the Connecticut attorney general.

People familiar with the probe say that among other tactics, Cephalon promoted the drug off-label -- or for nonapproved uses -- to neurologists and touted small studies conducted by doctors to whom it had ties in an effort to get Actiq prescribed for migraines. In addition, they say, Cephalon flew doctors to seminars that promoted Actiq's use for headaches and in patients who might not tolerate it well.

Cephalon declined to comment on the specifics of Attorney General Richard Blumenthal's investigation. Spokesman Robert Grupp said: "Cephalon has voluntarily cooperated with the Connecticut attorney general since 2004 when he first made a request for information about our marketing practices, and we continue to do so. Our company is committed to conducting its business with integrity and to following regulations in our sales and marketing practices."

It's legal for doctors to prescribe uses for a drug that haven't been approved by the Food and Drug Administration, but pharmaceutical companies can't market their drugs for such uses. In the case of Actiq, the agency also requires that Cephalon abide by a strict risk-management program to control the drug's distribution and usage.

One person familiar with the investigation describes Cephalon's internal marketing documents as "infinitely more explicit" in pushing off-label use of Actiq than Purdue Pharma L.P. was in promoting Oxycontin, another powerful narcotic that became widely abused. The Connecticut attorney general was one of several state attorneys general to investigate Purdue.

Mr. Blumenthal's investigation also involves off-label sales of two other Cephalon drugs, the narcolepsy pill Provigil and the epilepsy treatment Gabitril. Cephalon is also being investigated by the U.S. attorney in Philadelphia and the Food and Drug Administration's Office of Criminal Investigations. Like Mr. Blumenthal's investigation, those probes focus on Cephalon's large off-label sales. The U.S. attorney and the FDA declined to comment.

Mr. Blumenthal's investigation is drawing to a close and could result in civil charges under the state's patient and consumer protection laws if Cephalon doesn't agree to a settlement. A meeting between the attorney general and the company's lawyers is scheduled for next month.

If Cephalon opts to settle the case out of court, Mr. Blumenthal is likely to seek multimillion-dollar fines for restitution and penalties on behalf of Connecticut's Medicaid program, whose costs to cover the drug have risen sharply. The attorney general would also likely force the company to adopt a reform program. "We want them to change the way they do business," Mr. Blumenthal says.

Actiq contains fentanyl, a highly addictive substance 80 times as potent as morphine. Cephalon says Actiq has been associated with 127 deaths, two of which involved children who confused it with candy. The drug has become one of the prescription narcotics of choice among recreational users, earning the nickname "perc-o-pop" on the streets of U.S. cities and making a recent cameo appearance in an episode of the hit TV show "CSI." In the first nine months of this year, Actiq sales reached $471 million.

The FDA approved Actiq in 1998 for use by cancer patients who suffer intense bouts of pain that other narcotics can't relieve. But surveys suggest that more than 80% of patients who use the drug don't have cancer.

The trigger for Mr. Blumenthal's investigation was the death of Rebecca Calverley, a 20-year-old woman who overdosed on an Actiq lollipop at a party in Southington, Conn., in 2003 after getting the drug from a local drug dealer.

Mr. Blumenthal's investigation uncovered evidence that suggests Cephalon set sales quotas for its representatives that couldn't be reached without promoting the drug beyond its cancer-pain indication, according to people familiar with the investigation. Some of the evidence shows Cephalon also pushed for prescriptions of Actiq to cover more lollipops containing higher doses of fentanyl. Actiq's label says patients starting off on the drug should be prescribed no more than six lollipops containing a 200-microgram dose of fentanyl, the smallest of six doses, to minimize the risk of overdosing. Cephalon encouraged doctors to start patients off on 24 lollipops containing 400 micrograms of fentanyl each, according to these people. The higher dose costs more and brings in more revenue.

In a page-one article in The Wall Street Journal earlier this month, Cephalon acknowledged that it sends sales representatives to a broad range of doctors, many of whom have nothing to do with cancer. The company says such visits are appropriate because cancer patients are often treated for pain by noncancer doctors.

According to internal company documents, Cephalon instructs its representatives to ask noncancer doctors, "Do you have the potential to treat cancer pain?" Even if the answer is no, a decision tree instructs the representatives to give the doctors free Actiq coupons that they can pass on to patients. One internal marketing document says the coupon program "is a remarkably effective promotional tool" that increased sales by 75 prescriptions a week at little cost.

Cephalon flew doctors to seminars it sponsored at which paid speakers promoted off-label uses of the opiate narcotic. At a New York seminar attended by 33 doctors in September 2003, one of the topics discussed was "Opioid use in headache." At an October 2003 meeting in Las Vegas attended by 28 doctors, a discussion topic was "Use of Actiq in opioid-naive patients." Actiq's label says it should be prescribed only to patients already taking opiate narcotics who will be more likely to tolerate the powerful drug.

Mr. Grupp declined to comment on the seminars. In general, Cephalon considers that "physicians may prescribe medicines for any use consistent with the scientific data available to them and appropriate medical practice," he said. "The decision to prescribe 'off label' is theirs and theirs alone."

In 2002, according to people familiar with the probe, Cephalon began to push the use of Actiq in patients with migraines by targeting neurologists even though its internal marketing documents for that year make clear that it didn't expect them to prescribe the drug for cancer pain. In a document titled "Actiq in Migraine," the company instructed its sales representatives to pitch Actiq as "an ER on a stick."

Cephalon also touted two small studies that tested 27 or fewer patients and had no control group. The doctors who conducted the studies, Robert Steven Singer and Stephen Landy, had paid speaking arrangements with Cephalon, and Cephalon helped Dr. Landy with the study he conducted, according to the people close to Mr. Blumenthal's probe.

Dr. Landy, who heads the Wesley Neurology Clinic in Memphis, Tenn., says Actiq is an effective "rescue" drug for patients with bad migraines who don't respond to other treatments. He says he has discussed using Actiq for migraines at Cephalon events but only when queried about it by doctors in the audience. Dr. Landy won't say how much Cephalon paid him for speaking. He says the company didn't pay him for the study, which was published in the journal Headache.

Dr. Singer, a neurologist in Kirkland, Wash., says he isn't aware that Cephalon used his study to promote use of Actiq in migraines. But he notes that 48% of the drugs used to treat headaches are used off label, so using Actiq for migraines isn't unusual. He declines to say how much Cephalon paid him to speak.

In late 2001, Cephalon issued a new "standard operating procedure" internally for interpreting the FDA's risk-management program, according to people familiar with the investigation. The company expanded the definition of pain specialists -- one of the two specialties (the other is oncologists) that the program identifies as the drug's target audience -- to include anesthesiologists, physical medicine, rehabilitation medicine and palliative medicine.

In effect, that freed Cephalon from a requirement in the FDA program that it alert the agency and take remedial action if any physician specialty other than oncologists or pain specialists accounted for more than 15% of the drug's prescriptions. Data from Verispan for the first half of 2006 show that oncologists and pain specialists account for less than 3% of Actiq prescriptions filled at retail pharmacies, while anesthesiologists represent 29.5% of prescriptions.

Breast Implants Made Of Silicone Win FDA Backing

2006-11-21T12:30:00.000-08:00

Nearly 15 years after banning silicone breast implants in most cases, the Food and Drug Administration approved revamped versions at a time of soaring demand for cosmetic procedures.

Many of the original marketers, who lost billions of dollars in lawsuits related to allegedly flawed silicone implants, are long out of the business. Still, the FDA's approval late Friday will accelerate a push into aesthetic medicine by two companies that are heirs to the U.S. breast-implant business: Allergan Inc. and Mentor Corp.

Both companies are betting big on the burgeoning cosmetic-medicine market. They expect the new implants -- approved for cosmetic augmentation in women age 22 and older, and for reconstructive use in women of all ages -- to draw a generation of body-conscious buyers too young to remember the high-profile health concerns that silicone implants once sparked.

Still, the companies face a delicate task in overcoming the devices' long history of safety concerns. The FDA banned silicone implants for use in cosmetic augmentation surgery in 1992 amid complaints of rupturing and worries that they could lead to problems ranging from connective-tissue disorders to cancer. While those links were never confirmed, manufacturers set aside billions of dollars to pay out to women who sued over alleged injuries. The litigation drove many companies out of the business and helped push Dow Corning Corp. into bankruptcy.

Consumer groups have raised objections to silicone implants for years, saying there isn't enough evidence of their long-term safety. A 2000 report by the Institute of Medicine, an independent federal research organization, found no link between silicone implants and systemic neurological or connective-tissue diseases. Still, it concluded there was "cause for concern" about complications such as infections, scar tissue and leaking. Another 2000 study, by the FDA, found that of 344 women participating, two-thirds had ruptured silicone implants and showed no symptoms before the leaks were detected.

Allergan and Mentor are expected to soon launch marketing campaigns aimed at surmounting women's fears about the implants and pointing to the differences between their products and the ones largely banned by the FDA in 1992. The newer devices contain a thicker silicone gel that the companies say makes implants less likely to leak. An even firmer gel is used in more advanced technology implants that still are under FDA review; those recently were approved in Canada.

Both companies expect high demand. Allergan, of Irvine, Calif., in March acquired Inamed Corp., developer of the breast implants that Allergan now sells. Mentor, of Santa Barbara, Calif., in recent months has transformed itself into a purely aesthetic company by divesting unrelated operations. Both are developing rival injectables for facial rejuvenation, a category currently dominated by Allergan's Botox.

Since 1992, women seeking breast implants for cosmetic reasons have had to use saline implants, which are filled with salt water. They are generally viewed as less natural-looking because they can be too hard or become wrinkly if underfilled.

Demand for the new silicone implants may be tempered by costs. The FDA is recommending that patients get regular screening, including magnetic-resonance-imaging examinations every few years, to detect possible rupture and leaking silicone. Like other cosmetic surgery, implant surgery isn't covered by insurance. It is highly unlikely that screening tests would be covered. The FDA also warned that women who get the implants likely will need further surgery at some point because of issues including ruptures and hardening of breast tissue.

Currently, with saline implants, the total cost of breast augmentation surgery ranges from about $6,000 to $10,000. A set of silicone implants alone costs $1,600 -- twice the price of saline implants -- but prices could fall as the market shifts to cosmetic applications that aren't reimbursed by insurance.

Still, the availability of silicone implants seems likely to boost a breast-augmentation market that already is growing significantly. In Europe, where both types of implant are available, roughly 90% of sales are of silicone products. Plastic surgeons expect a similar pattern to develop in the U.S.

Before the controversy over silicone implants peaked in late 1991, an estimated 150,000 women a year underwent implant surgery, including 20% for breast reconstruction. The number of procedures plunged 60% the following year, according to statistics compiled by the American Society of Plastic Surgeons.

Last year, there were about 291,000 breast-augmentation procedures in the U.S., making such surgery the third most common cosmetic procedure behind liposuction and nose reshaping, according to the plastic surgeons group. More than 80% of breast-implantation surgeries last year were done for cosmetic reasons, the rest for reconstruction. Based on industry estimates, the annual implant market appears to be about $400 million, not including surgeons' fees.

Physicians and market experts say there could be a spurt in demand for cosmetic breast surgery now that the silicone implants can be marketed for cosmetic use. Growth predictions vary from 5% to more than 50%. Some plastic surgeons say they have lists of women waiting for silicone implants.

Given the longstanding health concerns, the FDA will require extensive studies, including that each company conduct a 10-year study that will include 40,000 women. The device makers also will have to track the implants to ensure patients can be notified of any problems. Daniel Schultz, the director of the FDA's device center, said FDA officials felt that in contrast to 1992, "we have data that has been reviewed extensively by the agency," which met the FDA's standard of providing a "reasonable assurance" of safety and effectiveness.

The implants remain a politically charged issue that could draw scrutiny from the newly elected Democratic-controlled Congress. Lawmakers already are likely to be examining the FDA's handling of medical devices, as they reauthorize the user fees that fund part of the agency's device budget. Connecticut Democrat Rosa DeLauro, who will head the House Appropriations subcommittee that oversees the FDA's budget, has proposed a bill that includes safety requirements for breast implants.

Roxanne Guy, a plastic surgeon in Melbourne, Fla., said patients will need "re-education to understand that the new-generation product is superior and not like the old one." She said the typical breast-implant patient is a married woman in her mid-30s who is finished having children and breastfeeding and now "wants to get back what was lost."

Both companies were "ready to ship the minute approval happens," said Jose Haresco, an analyst at Merriman, Curhan Ford & Co., recently. Mentor and Allergan have nearly equal shares of the U.S. market, though Mentor's share has been edging up this year. Breast implants account for more than 80% of Mentor's revenue, while they are a relatively small business for Allergan, a much larger, diversified company with eyecare and dermatology products.

Mr. Haresco said he expects the U.S. breast-implant market to expand to $600 million to $700 million in the next two to three years, assuming the companies can continue to charge about $1,600 for a set of silicone implants. Alex Arrow, an analyst at Lazard Capital Markets, is more cautious. He said the high price of silicone implants reflects their current use for breast reconstruction, an application that is covered by medical insurance. He predicts silicone-implant prices will fall as the silicone market shifts to a largely cash cosmetic business.

---

Silicone Saga Major developments in the history of silicone breast implants: 1980s: Women file lawsuits against makers of silicone breast implants, claiming they caused health problems. 1992: FDA bans silicone implants broad use. 1999: Institute of Medicine links silicone implants to local complications but not systemic health problems. 2003: FDA advisory panel backs bid by Inamed to widely sell silicone implants. 2004: FDA rejects Inamed's request to widely sell silicone implants and seeks more information. 2005: Another FDA advisory panel narrowly endorses approval of Mentor's implants, but rejects Inamed's. 2006: Botox maker Allergan buys Inamed.

Novartis Suffers 2nd Pipeline Setback In A Week

2006-11-21T12:27:00.000-08:00

Novartis AG (NVS) Friday experienced its second setback in less then a week, when the advisory panel of the European Union's drug regulator advised against approval of the Swiss pharmaceutical company's antifungal medicine Mycograb.

On Monday, Novartis had said that the U.S. Food and Drug Administration will take three months longer than anticipated to decide on approval for diabetes drug Galvus, because it is reviewing data on the safety and dosing of the drug that the company submitted only recently. Analysts still expect the potential multibillion dollar drug to gain approval, but the delay means its falling further behind Januvia, a rival treatment, for which its maker Merck Co. (MRK) has already gained the regulator's ok.

Now, the FDA's European counterpart said that its expert panel, the Committee for Medicinal Products for Human Use, or CHMP, was concerned about the quality and safety of Mycograb, an antifungal drug.

Novartis plans to submit additional data to the E.U. to support the approval of Mycograb, which is in development as a treatment for life-threatening fungal infections.

This submission for E.U. approval was made last year by NeuTec Pharma, a British pharmaceutical company that Novartis acquired in mid-2006 to expand its portfolio of compounds for hospital-acquired fungal and bacterial infections. The E.U. panel said data relating to the manufacturing and characterization of the product was insufficient to determine the safety of the compound.

Mycograb, is an antibody, which could generate annual revenue of $300 million, if approved, according to analysts' estimates. It is a so-called add-on treatment, which aims to improve the effectiveness of existing drugs.

Novartis said it is committed to working with the CHMP to determine appropriate next steps.

At 1650 GMT, Novartis was down CHF0.15, or 0.2%, at CHF72.35, in a lower broader market.

On a brighter note, the European Medicines Agency issued positive opinions on Novartis' eye drug Lucentis and hypertension medicine Exforge. Both drugs have the potential to become blockbusters with annual sales of $1 billion or more, analysts say. The European Commission usually follows these recommendations, and typically grants formal approval within 90 days.

Lucentis, or ranibizumab, has been shown to maintain or improves vision in patients with age-related macular degeneration, a form of bleeding behind the retina and the leading cause of blindness in elderly people.

Lucentis is approved in Switzerland and the U.S. for treatment of wet AMD.

AMD is an eye disease characterized by abnormal, leaky blood vessels that form under the retina, the light-sensing part of the eye. The vessels leak fluid into the eye, damaging the macula, the central part of the retina at the back of the eye. The macula is responsible for the straight-ahead vision necessary for everyday activities like reading, driving, watching television and identifying faces.

Lucentis is the first drug ever that has been shown to improve vision in people suffering from wet-form AMD.

The drug was developed by Novartis and Genentech Inc. (DNA), which is selling Lucentis in the United States. Novartis owns the marketing rights for the rest of the world.

The E.U. experts also recommended to approve Exforge, a pill that combines two different types of hypertension treatments.

Exforge combines Novartis' top-selling Diovan and amlodipine, a drug that lowers blood pressure in a different way, in a single pill. Amlodipine is the active ingredient in Pfizer Inc's (PFE) Norvasc, which will lose patent protection in September 2007.

Some analysts say the main advantage of Exforge to Novartis is that it will help protect Diovan sales when the bestseller loses patent protection in 2012. Peak sales estimates for Exforge start at around $500 million, though some analysts expect the drug to eventually generate annual sales of $1 billion or more.

Eisai, Pfizer To Challenge UK NICE On Aricept

2006-11-21T11:41:00.000-08:00

Japan's Eisai Co. (4523.TO) and Pfizer Inc (PFE) said Friday they will challenge the U.K. medical advisory body's recommendation to stop using the company's drug for treating mild cases of Alzheimer's disease, saying the organization hadn't disclosed enough information on the decision-making process.

Shire PLC (SHP), the U.K.'s third largest pharmaceutical company and maker of Alzheimer's drug Reminyl, also said it supports Eisai's and Pfizer's proposed challenge.

The Tokyo-based pharmaceutical company said it will seek a judicial review of the process by which the advisory body, the National Institute for Health and Clinical Excellence, or Nice, reached the decision to ban its Aricept drug for treating mild Alzheimer's disease.

Aricept, one of a small number of Alzheimer's disease treatments available, is Eisai's best-selling drug. Pfizer, a promotion partner for the drug, is joining Eisai in challenging Nice's guidance for the National Health Service.

"Nice has left no option but for us to proceed in this way to ensure that patients with Alzheimer's disease are protected from failures in process," Olivier Brandicourt, managing director of Pfizer U.K., said in a statement.

In a separate statement, Eisai said: "Nice has repeatedly refused to disclose a fully working version of the cost effectiveness model used to determine the value of treatment in patients with mild Alzheimer's disease".

Many of the conclusions drawn by Nice cannot be supported legally or are irrational, and these views are supported by patient groups, caregivers and medical experts, Eisai added.

Eisai and Pfizer will call on Nice to withdraw the recommendation in its "Final Appraisal Determination," or FAD, and postpone issuing the new guidance on Nov. 22, the Japanese company said.

They will seek the disclosure of cost effectiveness calculations used in Nice's evaluation and development of a new FAD.

This will be the first time a Nice decision has been contested at this level, Eisai said.

Eisai said it will submit a letter outlining the grounds for the judicial review request. Nice has 14 days to respond, after which Eisai can apply to the High Court for permission to proceed to judicial review.

In an emailed statement, Nice said it plans to respond to Eisai's letter and "act appropriately in any court proceedings which may follow."

However, the drug advisory body said it still expects to publish its recommendation on the care for all types of dementia and the use of drugs for treating Alzheimer's disease on Nov. 22.

Eisai has been marketing Aricept as a treatment for mild and moderate cases of Alzheimer's disease in the U.S., Japan and other markets. It recently received U.S. approval to use the drug to treat severe cases of the disease.

Eisai's and Pfizer's move follows an announcement by Nice last month, when the advisory body said an appeal against its recommendation to restrict the use of Alzheimer's drugs to patients with a moderate form of the disease had been rejected.

Swiss drugmaker Novartis AG (NVS), which markets Alzheimer's drug Exelon, one of the drugs which use was restricted, did not appeal against NICE's recommendation, a spokesman said.

Naproxen Tied To Greater Risk Of Heart Attacks

2006-11-21T11:39:00.000-08:00

A disputed government study of common painkillers found that naproxen increased the risk of heart attack and other cardiovascular events compared with a fake pill, according to data published yesterday, nearly two years after the study was halted.

The study's results relate to whether naproxen, which is sold over the counter as Aleve by Bayer AG of Germany, is as safe as is commonly believed. The results didn't point to a clear conclusion. The class of drugs to which naproxen belongs is generally considered to carry some heightened cardiovascular risks. This study's results "provide some support" for that theory, the study's authors wrote, but added that "the measure of this risk remains a matter of speculation."

Bayer said in a statement the "overwhelming body of scientific evidence" supports naproxen's safety. The company also noted the study involved long-term use of naproxen to ward off Alzheimer's disease, which isn't consistent with Aleve's intended use as a short-term pain reliever.

The study found the cardiovascular risk of Pfizer Inc.'s Celebrex painkiller wasn't meaningfully higher than that associated with a fake pill, or placebo.

The detailed data published for the first time yesterday showed that about 2,500 seniors across the U.S. participated in the study. Those on naproxen experienced cardiovascular death, heart attack, stroke, congestive heart failure and transient ischemic attack at a rate 63% higher than those in the placebo group. Those on Celebrex had a 10% greater risk of such events than in the placebo group.

The results were published online by Public Library of Science, a San Francisco nonprofit group. The results were more detailed than findings cited in the government's announcement of the study's halt in December 2004.

The study's authors cautioned that the naproxen data weren't definitive due to the study's early termination. A leading cardiologist blasted the findings, accusing the National Institutes of Health of improperly terminating the study and making it impossible to interpret the results reliably.

The suggestion of a heart risk for naproxen runs counter to previous studies indicating it is among the safest on the heart of all nonsteroidal anti-inflammatory drugs, or NSAIDs, a class of drugs that include ibuprofen and diclofenac. The dispute surrounding the NIH study likely means the debate about the heart risks of NSAIDs will continue. The debate gained full force after Merck & Co. pulled its Vioxx painkiller from the market in 2004 over cardiovascular-safety concerns.

The NIH's National Institute on Aging started the Alzheimer's Disease Anti-Inflammatory Prevention Trial, or Adapt, in 2001 to test whether naproxen and Celebrex were effective in preventing Alzheimer's dementia or delaying cognitive decline in elderly people. Both drugs were compared with a placebo. Merck pulled Vioxx off the market after it was linked to elevated risks of cardiovascular events. As concern increased about the safety of drugs related to Vioxx, including Celebrex, a number of studies that included them were halted -- including the Adapt trial.

Genentech Gets OK For Expanded Use Of Cancer Drug

2006-11-21T11:37:00.000-08:00

Genentech Inc. (DNA) said Thursday that it won Food and Drug Administration approval for its drug Herceptin to treat early-stage, HER2-positive breast cancer.

Herceptin is currently approved in the U.S. to treat advanced HER2-positive breast cancer, an aggressive form of the disease found in women who test positive for a protein known as HER2.

It is estimated that about 200,000 women are diagnosed with the breast cancer per year. Of those, about 25% are HER2-positive.

Approval came nine months after the South San Francisco, Calif., biotechnology company filed the request with the FDA. The agency was set to issue a decision in August, but it opted to extend the deadline after it requested additional information from the company.

"We believe that this (approval) represents such an enormous improvement for women with breast cancer," David Schenkein, the company's vice president of clinical hematology and oncology, told Bulresearch.

Schenkein said the company submitted the application based on results from two trials involving a total of 3,500 women with early, HER2-positive breast cancer. The primary endpoint was risk reduction for recurrence of the disease.

According to him, recurrence risk was cut by more than half with Herceptin, "which actually represents perhaps the largest improvement in outcome for women with breast cancer in 25 years." Schenkein also said the drug improved overall survival.

U.S. sales of Herceptin were of $747.2 million for 2005 and $912 million for the nine months ended Sept. 30. Genentech said in its latest quarterly report that increased sales of the drug this year are attributed to facts including off-label use for treatment of early-stage HER2-positive breast cancer.

A company spokeswoman declined to provide revenue expectations with the new FDA approval.

In Europe, where Herceptin is sold by Genentech parent company Roche Holding AG (RHHBY), the treatment gained approval for patients with early-stage HER2-positive breast cancer in May.

Neuroprotectant Therapy Faces Uphill Battle After Failure

2006-11-21T11:30:00.000-08:00

The necropolis of neuroprotectant drug candidates has a new resident, which is terrible news for stroke patients as well as those looking for the next pharmaceutical blockbuster.

The recent failure of the only late-stage neuroprotectant candidate, a type of drug that seeks to protect the brain from further damage after a stroke, has led some to declare that the drugs are a myth, but prominent neurologists disagree. A neuroprotective therapy could save lives and lessen the severity of many strokes, but also see such widespread use that its global sales would be measured in billions.

"There is a sense of desperation out there," says Caroline Stewart, an analyst with Piper Jaffray, "because neuroprotectants have been such a graveyard for drug development."

Stroke kills about 5.5 million people every year, according to the World Health Organization, and is the third most common cause of death in developed countries behind heart disease and cancer. Even where advanced technology and facilities are available, almost two-thirds of stroke victims die or become dependent.

One hope for the future, Renovis Inc.'s (RNVS) neuroprotectant candidate NXY-059, died in late October when it missed every endpoint in its second Phase III study. The first Phase III had raised the hopes of the medical community, as well as Wall Street, for the drug's ultimate success. The news destroyed the company's share price - now trading based on the value of the cash it holds - and left it with a relatively thin pipeline following a string of clinical failures.

Renovis's partner in the drug, British pharmaceutical giant AstraZeneca PLC (AZN), walked away in disgust after the debacle of SAINT II - the study's official name - leaving virtually no future for NXY-059 and sending shock waves to those in search of similar therapies.

AstraZeneca declared that the SAINT II trial was a landmark study in determining that neuroprotectants simply don't work and that the company abandoned the search for similar drugs.

"The people that we've worked with in the outside world, the opinion leaders, think that this really has shown them that the models that they use and the work that they've done to try and generate drugs like this, is not valid," said Dr. John Patterson, the executive director of development at AstraZeneca.

"We're talking more generally about neuroprotection and the ability for anything, whether it's a free radical trapping agent or another mechanism, to do something in man that's meaningful," he added.

Currently, the only companies with stroke neuroprotectant drugs in development are Germany's Paion AG (PA8.XE) with Enecadin and Israel's privately held D-Pharm with DP-b99, both of which are in Phase II trials.

The Long Search

Failure is not a new development in the world of neuroprotectants; none of the more than 1,000 different drug candidates tested since 1957 have made it to the market, according to a paper published in the March issue of Annals of Neurology.

In light of the number of failures, an academic and industry group published the Stroke Therapy Academic Industry Roundtable criteria, or STAIR, in 1999 to ensure that only viable neuroprotectant candidates proceeded to costly advanced clinical trials.

Renovis's NXY-059 is the first drug to meet all of the STAIR criteria and was viewed as having a promising future as a blockbuster among a field of no competition.

The only other stroke drug on the market is a clot-dissolving drug, or thrombolytic, known as tissue plasminogen activator, or tPA, which can only be used within the first three hours of a stroke. Prior to using tPA, doctors must conclude that the stroke is caused by a clot - the cause of about 80% of strokes - and not a hemorrhage because the drug can increase bleeding.

When, a stroke occurs, blood flow to a region of the brain is cut off, launching a cascade of events that kills brain cells and releases toxic free radicals that cause additional cells to perish over the ensuing hours and days.

The challenge is to restore blood flow to the struggling cells, usually by administering tPA to help remove the blockage. Theoretically, a neuroprotectant will halt the cascade, and provide the greatest benefit when used in concert with tPA.

Some neurologists feel that future success will be found through a combination therapy, possibly tPA with one or many neuroprotectant agents as well as hypothermia, which cools the brain to inhibit continued damage.

"I think a single molecule directed at a single mechanism will not work," said Dr. Patrick Lyden, director of the UCSD/VA Stroke Center in San Diego and North American coordinator for SAINT II. "If you look back at the last 20 years, we have one failure after another. They were all single-bullet approaches."

Dr. David Howells, the senior author of the Annals of Neurology paper and head of the Neuroregeneration Laboratory at the University of Melbourne in Australia, feels that neuroprotectants have performed poorly in trials because the methodology that met success in animal models wasn't adequately replicated in human trials.

"Neuroprotection isn't dead, because the neuroprotective hypothesis - that blocking cell death pathways in the very acute stages of stroke can save brain [cells] - has never been adequately tested in clinical trials," said Dr. Howells. He notes that reproducing the laboratory model would prove very difficult amid commercial pressures for quick results that are applicable to large numbers of patients.

Both Dr. Lyden and Dr. Howells stress that decreasing the amount of time it takes to get patients to treatment is the most important factor to improving both stroke therapy and clinical trials of neuroprotectants. They even note that previously unsuccessful trials, including SAINT II, might show different outcomes if such a change is made.

"We can boost the treatment rate from 4% to 20% right now with no new treatments" Said Dr. Lyden. He notes that in most areas, emergency responders are required to bring patients to the closest hospital, regardless of that hospital's facilities, instead of a stroke center where they can possibly receive tPA within three hours.

A Theoretical Blockbuster

If a neuroprotectant eventually reaches the market, analysts agree that it will be worth billions in yearly sales. Neuroprotectant candidates tend to be very safe, allowing for widespread administration and translating into high sales volume.

"Estimates varied from $1 billion-$3 billion worldwide for NXY-059," says Caroline Stewart, an analyst with Piper Jaffray who notes that the range was indicative of people's opinion of its approval prospects.

Now that NXY-059 has continued the tradition of failure, that huge market may not be tapped for a while as analysts expect a long lull in development.

"In general, early development companies should think twice after SAINT II and the strong statement from AstraZeneca," said Elemer Piros, a biotechnology analyst with Rodman & Renshaw, who notes that smaller companies are dependent on the major pharmaceutical companies to fund the large trials necessary to test neuroprotectants.

Piros says that throughout the history of failed neuroprotectants, almost every big company in the industry has tinkered with the idea due to the lure of the potentially huge payoff.

Despite this temptation, it is likely that the failure of NXY-059 will at least temporarily scare companies from investing to develop similar drugs.

FDA To Discuss Safety Of 16 Drugs In Children

2006-11-21T11:28:00.000-08:00

WASHINGTON -- A Food and Drug Administration panel is set to meet today to discuss the safety review of 16 drugs, including flu drug Tamiflu, in pediatric patients.

The pediatric advisory committee will evaluate new and updated reports by the FDA staff that include information on the drugs' safety compiled over a year. The panel will then make recommendations that could include label changes or further investigation of adverse events.

The FDA isn't required to follow the panel's suggestions, but it usually does.

Although the panel today is to issue an opinion on Tamiflu's label, on Tuesday the drug's manufacturer, Roche Holding AG, said it would follow the FDA staff's recommendation in the report and update the label to warn patients of potential abnormal behavior during treatment, including delirium and hallucinations.

In its report, the staff said the label should be changed following a review that found 103 cases of "neuropsychiatric adverse events," including the death of a 14-year-old boy who fell after climbing on his condominium balcony's railing.

According to documents posted on the FDA Web site ahead of today's meeting, eight drugs under review didn't raise any safety concerns. They include cholesterol-lowering medications Lipitor from Pfizer Inc. and Zocor from Merck & Co., Eli Lilly & Co.'s cancer drug Gemzar, and Johnson & Johnson's Ditropan to treat bladder instability.

The other eight drugs either presented new unlabeled safety concerns or "other attributes," including labeled but "serious adverse events of interest" and past safety concerns, the FDA said.

Novartis Looks To Chinese Medicine For New Drugs

2006-11-15T13:06:00.000-08:00

In Xinjiang province in China's remote and mountainous west, botanist Shen Jingui was searching for a snow lotus, a grayish-white flower used for centuries in Chinese medicine to alleviate the symptoms of premenstrual syndrome. He spotted the plant on a rock ledge and shimmied across to pick it. He slipped and plunged some 30 yards, slamming into rocks on the way down.

When he regained consciousness, local farmers were putting him on a horse to take him to the nearest health clinic, several hours away. "I was very scared," he recalls of the incident, "but I was happy to collect the material."

Mr. Shen, head botanist for the Shanghai Institute of Materia Medica, a government-funded laboratory, has spent three decades trekking across China and going to great lengths to ferret out rare plants and herbs traditionally used in treatments for ailments ranging from aches and pains to cancer.

His bag of plants has captured the interest of Swiss drug giant Novartis AG, which since 2000 has invested several million dollars in a venture with SIMM. Last month, Novartis struck a similar deal with the Kunming Institute of Botany, an organization that works with traditional remedies in the country's southwestern Yunnan province. Earlier this month, Novartis announced it will invest about $100 million in its own pharmaceutical research-and-development center in Shanghai.

Facing soaring costs in developing new drugs and a limited pipeline of promising candidates, Novartis hopes that traditional Chinese medicines will hold the secrets for a new generation of blockbusters to fight diseases such as Alzheimer's. While Novartis isn't the only multinational drug company seeking to tap traditional Chinese cures -- French drug maker Servier also has a collaboration with SIMM -- Rachel Lee, a senior manager at Boston Consulting Group in Shanghai, says "no other major pharma has gone further than Novartis" in this area.

The collaboration between East and West on drug development is in many ways an unlikely one. Chinese and Western specialists approach pharmacology from very different angles. For centuries, Chinese doctors have tinkered with different mixtures of medicines, guided in part by trial and error, to see which ones are most effective. Working with that body of knowledge, they operate on the assumption that the traditional remedies work, even if by Western scientific standards it's not completely clear why. Chinese doctors "know it will cure people, but they don't know what target it hits," says Shen Jingkang, a professor at SIMM.

In contrast, researchers at Western pharmaceutical companies often begin the search for a drug by identifying a target, and then look for a chemical compound that has the desired effect. If they do find a drug that works, they usually understand the mechanism behind it. That helps in refining the compound to make it more effective and in convincing regulatory authorities such as the U.S. Food and Drug Administration that the medicine is safe and effective.

Novartis hopes to isolate the particular compounds active in the Chinese traditional medicines by testing the raw extracts from plants collected by Mr. Shen and fellow botanists.

"There are so many compounds in nature, from the seas to the jungles, it's very difficult to know where to start," says Paul Herrling, the head of corporate research at Novartis. "China has thousands of years' experience of using plants in Chinese traditional medicines. The idea was, why not use the Chinese experience as a kind of filter?"

Novartis has experienced the potential of Chinese traditional medicines firsthand. The company's malaria drug Coartem stems from a traditional Chinese cure for fever. Mention of the plant, Artemisia annua L. or sweet wormwood, was found in a Chinese medicine book written on silk, unearthed from a tomb of the West Han Dynasty, which began around 200 B.C. Chinese military scientists developed the drug from the plant in the 1970s to treat Chinese soldiers suffering from malaria in Vietnam. In the early 1990s, Novartis struck a deal with the Chinese to purchase the rights to Coartem, a combination of a derivative of the plant and another antimalarial treatment, paying a few million dollars up front and royalties on future sales. Novartis declined to reveal the revenue it makes on the drug, most of which it sells to developing countries at $1 per treatment.

Since the venture began, Novartis says SIMM has provided around 1,000 natural products to the Swiss drug company's laboratories in Basel. In return, Novartis has agreed to pay SIMM royalties and fees if certain plants yield marketable pharmaceuticals.

So far, nine of the compounds have shown particular promise against specific disease targets, and two have been selected for further study, according to Dr. Herrling. While those numbers may seem small, the search for drugs using conventional methods is far less fruitful, he says. The investment is also small when stacked up against Novartis's typical research-and-development outlays.

In this particular project, it all goes back to a small group of botanists led by Mr. Shen -- before any research can begin in the lab, they must venture out in the field and find the plant.

On a recent afternoon at the laboratory in Shanghai, Mr. Shen dried lily bulbs and snow pine branches in small, neat piles on the floor of a sun-soaked hallway. He says he decided on this line of work when, as a student at a Shanghai university, he saw a film about the life of a Chinese botanist. The movie had a sad ending: The botanist dies after an accident collecting plants in a remote area and is carried home on the back of a horse. Nevertheless, Mr. Shen found the story inspiring.

"I love this career," says Mr. Shen, whose forearms and legs are covered with scars from his arduous trips to collect rare plants.

One of his most memorable finds was in spring 1999. Shortly after the snows melted, he set out on a weeklong journey to western China's remote Qinghai plateau. He was searching for a certain type of Aweto, an exceedingly rare fungus that Chinese-medicine doctors believe helps strengthen the immune system and fend off cancers. When dried, it looks like a small light-brown caterpillar.

Mr. Shen hired a guide and set off on horseback into the mountains, armed with descriptions from old Chinese texts. Deep in the forest, he spotted something, and got off his horse for a closer look.

"We won! We finally got it!" he recalls shouting as he jumped up and down. "I was screaming, 'I found it -- I found it!'" Gathering hundreds of bunches, he put them in his bag for the journey back to Shanghai.

Drug Pipeline Database free of charge

2006-11-15T05:35:00.000-08:00

Since November 13 is the Drug Pipeline Database of Bulresearch, free of charge.

There are over 3000 projects of drugs in development of more than 600 pharmaceutical and biotech companies.

The drug pipeline database is updated on weekly basis.

You can also viist the http://www.chartsbank.com for other resources regarding pharmaceutical marketing data and pharmaceutical sales force issues, case studies etc.

US Extends Review On Diabetes Drug Galvus 3 Months

2006-11-14T12:36:00.000-08:00

Swiss drugmaker Novartis AG (NVS) said Monday it is submitting further data to the U.S. Food and Drug Administration on the safety of its diabetes drug Galvus, meaning that the U.S. regulator's decision on approving the product will probably come at the end of February, three-months later than expected.

Novartis, based in Basel, said the additional data being submitted to the FDA provide further evidence, and confirm data submitted earlier, showing that skin findings identified in a single species during a preclinical animal study have not been seen in clinical studies with patients treated for type 2 diabetes.

The FDA late in 2005 had asked for such data for drugs belonging to a class of drugs to which Galvus belongs, so-called DPP4-inhibitors, Novartis spokesman John Gilardi said.

Galvus is one of Novartis' most important pipeline products, with expected annual sales of at least $1 billion.

Isis Cholesterol Drug Promising In Mid-Stage Trials

2006-11-14T12:33:00.000-08:00

Isis Pharmaceuticals Inc. (ISIS), Carlsbad, Calif., said an experimental drug for treating high cholesterol showed promise in mid-stage trials.

The drug, known only as "Isis 301012," proved effective in lowering blood levels of low-density lipoprotein - the so-called "bad" cholesterol - and related molecules such as triglycerides when administered alone or in combination with cholesterol-fighting drugs called statins.

Isis 301012, however, still hasn't demonstrated long-term safety, a task that could take several years. Some doctors worry that the drug, which blocks the production of an intermediate cholesterol molecule called ApoB-100, may leave fat trapped in the liver. If proven safe and effective, Isis 301012 could be one of the first practical applications of a so-far unproven drug technology called antisense, which aims to treat disease by blocking the function of individual genes.

Merck Scales Back FDA Application For Painkiller

2006-11-14T12:31:00.000-08:00

Merck & Co. will seek U.S. Food and Drug Administration approval for a narrower use of painkiller Arcoxia than it had previously sought, the drug maker said.

FDA approval of Arcoxia has been delayed for several years in the wake of safety concerns about the class of drugs to which it belongs, known as selective Cox-2 inhibitors. Arcoxia, which is approved for sale in 62 other countries, is Merck's follow-up to Vioxx, the Cox-2 inhibitor it pulled from the market in 2004, after a study showed it elevated heart-attack risk.

Merck, of Whitehouse Station, N.J., plans for now to seek FDA approval of two dose levels of Arcoxia to treat symptoms of osteoarthritis. Previously, it had sought a range of other uses, including treatment of rheumatoid arthritis and other conditions. The company said it would continue efforts to seek FDA approval for other doses and uses of Arcoxia.

Merck said Friday that it submitted a formal response to previous FDA communications about Arcoxia, which is expected to set in motion an FDA review lasting until April 2007.

Merck first applied for FDA approval of Arcoxia in 2001, submitting data from studies for uses such as relief of the signs and symptoms of osteoarthritis and rheumatoid arthritis, and management of acute and chronic pain. The company later withdrew its original application, because it wanted to resubmit one that sought an additional use -- treating a spinal disorder known as ankylosing spondylitis -- which it did in 2003.

In October 2004, just weeks after Merck withdrew Vioxx from the market, the FDA issued an "approvable letter," saying it needed additional safety and efficacy data before it could approve Arcoxia.

That additional safety data include a group of studies known as the Multinational Etoricoxib and Diclofenac Arthritis Long-Term program, or Medal. In August, Merck said preliminary Medal data showed that the rate of confirmed thrombotic cardiovascular events such as heart attack was similar between Arcoxia and diclofenac, an older painkiller sold as Voltaren by Novartis AG of Switzerland.

But the preliminary data also showed that people on Arcoxia discontinued the drug as a result of the side effect of high blood pressure at a greater rate than those on diclofenac.

Heart specialists and other experts have criticized the design of the Medal studies, because diclofenac itself has been linked to a higher risk for cardiovascular events than some other painkillers.

Merck has insisted the comparison to diclofenac was appropriate, because it is a widely used treatment.

Novartis Painkiller Prexige Stages A Comeback

2006-11-14T12:02:00.000-08:00

Swiss drugmaker Novartis AG (NVS) Tuesday said it will start selling its painkiller Prexige in the European Union next year, marking the return of a drug that many analysts had considered dead.

Prexige belongs to the same class of drugs as Vioxx, which maker Merck & Co. (MRK) in 2004 withdrew from the market after a study showed it increased the risk in some patients of heart attacks and strokes.

This type of drug, known as Cox-2 inhibitors, was developed to be gentler on the stomach than traditional pain relievers, such as ibuprofen and naproxen. These conventional pain medications belong to a class of drugs called nonsteroidal anti-inflammatory drugs, or NSAIDs.

After the Vioxx debacle, Novartis suspended the filing process for Prexige in Europe.

Since then, initial approval for Prexige - also known as Lumiracoxib - was granted in the U.K., where it has been available since December 2005. With all 26 member agreeing to issue national approval, Prexige can now go on sale in the E.U. for the treatment of ostheoarthritis, a leading cause of chronic pain.

The Basel-based company plans to refile Prexige for U.S. approval next year, meaning it could go on sale there in 2008 at the earliest.

Novartis underlined that Prexige was both effective and safe, but many analysts remain skeptical about the drug's potential.

"Although Prexige appears to have a better safety profile than Vioxx, general practitioners will remain cautious, and probably continue to prescribe NSAIDs, even though this class of drugs has its own safety issues," said Paul Diggle, analyst at Nomura Code Securities in London, who has a buy rating on Novartis.

NSAIDS are available in cheap generic versions - another reason why physicians will in most cases prefer to prescribe these older drugs, Diggle said.

For its part, Novartis highlighted the safety issues associated with these traditional pain relievers.

"Many patients can't tolerate the gastrointestinal side effects associated with NSAID pain treatments," said Dr. Gerd Burmester, Professor of Medicine at the Humboldt University in Berlin, and an investigator on one of the Novartis-sponsored studies on Prexige.

"Lumiracoxib has been extensively studied for both efficacy and safety, and has the potential to provide a valuable new treatment option for physicians."

Until two years ago, Novartis had bet on Prexige to become a blockbuster product with annual sales of $1 billion or more. Then Merck pulled Vioxx from the market, and the whole class of drugs to which it belonged came under scrutiny.

Most analysts remain cautious on Prexige's potential, despite the drug's strong showing in human testing.

"The whole class has been tainted," said Navid Malik, analyst in London at brokerage Collins Stewart, who has a hold rating on the stock.

"I don't think it will become a big product, and the FDA will proably be taking a very cautios view, and may grant it market permission only with a restricted label."

The news had little impact on Novartis shares, because the approval had been expected for the fourth quarter.

At 0940 GMT, Novartis shares were down CHF0.40, or 0.5%, at CHF76.40, while the broader Swiss market was also lower.

Company Web Site: http://www.novartis.com

Drug Pipeline Series: Approvals, Nov 6 - Nov 13, 2006

2006-11-14T08:36:00.000-08:00

Noxafil® (Posaconazole) Oral Suspension Approved in European Union for Prevention of Invasive Fungal Infections
Schering-Plough Corporation announced that the European Commission has granted marketing approval to NOXAFIL® (posaconazole) Oral Suspension for prophylaxis (prevention) of invasive fungal infections (IFIs) in the following patients at high risk of developing these infections: patients receiving remission-induction chemotherapy for acute myelogenous leukemia (AML) or myelodysplastic syndromes (MDS) expected to result in prolonged neutropenia and hematopoietic stem cell transplant (HSCT) recipients who are undergoing high-dose immunosuppressive therapy for graft versus host disease (GVHD).

The European Commission also approved NOXAFIL for oropharyngeal candidiasis (OPC) as first-line therapy in patients who have severe disease or are immunocompromised, in whom response to topical therapy is expected to be poor. OPC is a fungal infection of the mouth and throat.

The Commission approval of the prophylaxis and OPC indications for NOXAFIL results in Marketing Authorization with unified labeling that is valid in the current European Union (EU) 25 member states as well as in Iceland and Norway. NOXAFIL was previously approved in the EU and Australia for the treatment of certain IFIs in adult patients with disease that is refractory to or in patients who are intolerant of certain commonly used antifungal agents.

Medicis and Dow Pharmaceutical Sciences Announce FDA Approval of Ziana (Clindamycin Phosphate 1.2% and Tretinoin 0.025%) Gel
Medicis and Dow Pharmaceutical Sciences, Inc. announced that the U.S. Food and Drug Administration ("FDA") has approved ZIANA™ (clindamycin phosphate 1.2% and tretinoin 0.025%) Gel. ZIANA™ Gel is the first and only combination of clindamycin and tretinoin approved for once daily use for the topical treatment of acne vulgaris in patients 12 years or older. ZIANA™ Gel is also the first and only approved acne product to combine an antibiotic and a retinoid. ZIANA™ Gel contains clindamycin phosphate 1.2% and tretinoin 0.025%, formulated as a cosmetically elegant topical gel. ZIANA™ Gel has an alcohol-free, aqueous base. Medicis expects product supply to be available for shipping to wholesalers in the fourth quarter of 2006, and anticipates promotion and sample distribution of ZIANA™ Gel to physicians shortly thereafter.

FDA Approves MIRAPEX for the Treatment of Moderate-to-Severe Primary Restless Legs Syndrome
Boehringer Ingelheim Pharmaceuticals, Inc. announced that the U.S. Food and Drug Administration (FDA) has approved Mirapex® (pramipexole dihydrochloride) tablets for the treatment of moderate-to-severe primary Restless Legs Syndrome (RLS). RLS is a common, yet often undiagnosed, neurological sensorimotor disorder. While symptoms can vary from person to person, they are typically described as an urge to move the legs accompanied by burning, creeping, crawling, aching, tingling, or tugging sensations in the legs. Symptoms begin or worsen during periods of rest or inactivity -- for example, when lying down or sitting in a movie -- and generally are worse at night. Up to ten percent of the U.S. adult population is affected by RLS.

The FDA approval was based on safety and efficacy data from four randomized, double-blind, placebo-controlled clinical trials involving approximately 1,000 patients with primary moderate-to-severe RLS who were administered MIRAPEX (0.125mg, 0.25mg, 0.5mg and 0.75mg) or placebo once daily, 2-3 hours before going to bed. In controlled clinical trials, patients were treated with MIRAPEX for periods of three weeks up to nine months. In clinical studies, patients taking MIRAPEX experienced statistically and clinically significant improvements in short- and long-term efficacy versus placebo. In three clinical studies, the mean change from baseline in total International RLS Rating (IRLS) scores for patients treated with MIRAPEX demonstrated a statistically significant greater improvement compared with placebo-treated patients. In a fourth study, efficacy was sustained with MIRAPEX over a period of nine months, including a six-month open label treatment period followed by a 12-week placebo-controlled withdrawal period.

EPIX WINS CANADIAN APPROVAL FOR VASOVIST
Epix Pharmaceuticals announced that Health Canada has approved its novel blood pool imaging agent Vasovist for marketing in Canada. Vasovist (gadofosveset trisodium injection) is indicated for contrast-enhanced magnetic resonance angiography for visualization of abdominal or limb vessels in patients with suspected or known vascular disease.
Epix received a letter from the FDA in August denying the company's formal appeal to approve Vasovist and turning down its request for an advisory committee review of the agent. The company had submitted the appeal in June in response to two approvable letters for Vasovist.
The European Medicines Agency in 2005 granted marketing approval for Vasovist in all 25 members of the European Union. The agent has also been approved in Norway, Iceland, Switzerland, Australia and Canada.

Drug Pipeline Series: Submissions, Nov 6 - Nov 13, 2006

2006-11-14T08:35:00.000-08:00

IDM Pharma Submits Filing for European Market Approval of Mepact™ (mifamurtide, Junovan™ in the US) in the Treatment of Osteosarcoma
IDM Pharma announced that the company has submitted a Marketing Authorization Application (MAA) in eCTD format (electronic common technical document) to the European Medicines Agency (EMEA) for Mepact (mifamurtide for injection), requesting approval for its use in the treatment of patients with newly diagnosed resectable high-grade osteosarcoma following surgical resection in combination with post-operative multi-agent chemotherapy. This announcement follows the October 25, 2006 submission of a New Drug Application (NDA) for Junovan (mifamurtide for injection) to the Food and Drug Administration (FDA) in the United States.
As a result of the filing and after administrative validation of the submission, the EMEA Committee for Medicinal Products for Human Use (CHMP) will evaluate the application to determine whether to recommend to the European Commission the approval of Mepact in all the member states of the European Union. Mepact was granted Orphan Drug status by the EMEA in 2004.

Drug Pipeline Series: Phase III, Nov 6 - Nov 13, 2006

2006-11-14T08:21:00.000-08:00

NOVELOS BEGINS ENROLLMENT IN LUNG CANCER STUDY
Novelos Therapeutics announced that the first patient has been enrolled in the pivotal Phase III trial in advanced non-small-cell lung cancer (NSCLC) for its lead product NOV-002 in combination with first-line chemotherapy.
This randomized, open-label, international trial is being conducted under a special protocol assessment and will study 840 patients with Stage IIIb/IV NSCLC. It will evaluate NOV-002 in combination with paclitaxel and carboplatin versus paclitaxel and carboplatin alone. The trial, with a primary efficacy endpoint of improvement in median overall survival, will be conducted across approximately 100 clinical sites in 10 countries. Novelos is planning for patient enrollment to be completed in the first quarter of 2008.
NOV-002 is a small-molecule drug based on oxidized glutathione that acts as a chemoprotectant and immunomodulator. In a controlled, randomized Phase I/II clinical trial, advanced NSCLC patients treated with NOV-002 in combination with paclitaxel and carboplatin demonstrated improved objective tumor response and higher tolerance of chemotherapy versus the control group. In a controlled, randomized Russian trial, when used in combination with cisplatin-based chemotherapy, NOV-002 increased the one-year survival of advanced NSCLC patients from 17 percent to 63 percent.

OXFORD BIOMEDICA INITIATES TRIAL OF TROVAX IN RENAL CANCER
Oxford BioMedica has announced the start of TRIST, a pivotal, multicenter Phase III trial of TroVax, the company's cancer immunotherapy, in patients with advanced or metastatic renal cell carcinoma (RCC).
TRIST is designed to evaluate whether TroVax immunotherapy, added to first-line standard of care therapy, prolongs the survival of patients with locally advanced or metastatic, clear-cell renal carcinoma. The trial is a randomized, placebo-controlled, two-arm study that will compare TroVax in combination with standard of care to placebo with standard of care. The standard of care therapies will be interleukin-2, interferon-alpha or Sutent (sunitinib).
Approximately 700 patients will be recruited from about 120 centers in the U.S., the European Union and Eastern Europe. The primary endpoint for the trial is survival improvement, and secondary endpoints include progression-free survival, tumor response rates and quality of life. The protocol includes the appointment of a safety and efficacy monitoring board to assess the safety and potential efficacy of the drug combinations at various time points during the trial.
Median survival for patients with advanced or metastatic RCC is approximately 11 months, according to the company. The duration of the trial will be determined by the number of survival events (deaths) in the study group. The trial is expected to reach a conclusion in 2008 to 2009, which would support the company's objective of reaching product registration in 2009.
In May the company and the FDA reached a special protocol assessment (SPA) agreement for the TRIST study. The SPA agreement ensures that the design, conduct, analysis and endpoints of the trial are all acceptable to the FDA.

Drug Pipeline Series: Phase II, Nov 6 - Nov 13, 2006

2006-11-14T08:17:00.000-08:00

Callisto Pharmaceuticals Initiates Phase II Clinical Trial of Atiprimod in Advanced Carcinoid Cancer
Callisto Pharmaceuticals, Inc. announced the first dosing of patients in a multi-center, open-label Phase II clinical trial of Atiprimod to treat low to intermediate grade neuroendocrine carcinomas including advanced carcinoid cancers. The first study site to enter this trial is the Hematology Oncology Services of Arkansas in Little Rock, Arkansas, under the direction of Brad Baltz, M.D., the principal investigator. Several major cancer centers are currently reviewing the trial protocol and the Company anticipates that these sites will open in the near future.

The primary objective of the Phase II clinical trial is to evaluate efficacy of Atiprimod in patients with low to intermediate grade neuroendocrine carcinoma who have metastatic or unresectable cancer and who have either symptoms, despite standard therapy (octreotide), or progression of neuroendocrine tumors. Patients, after signing an informed consent, are required to complete two weeks of a symptoms diary to establish their symptoms baseline before commencing Atiprimod dosing. A maximum of 40 evaluable patients will be enrolled in this trial.

Osiris Therapeutics Reports Positive Phase II Results Using PROCHYMAL™ for the Treatment of Acute Graft vs. Host Disease
Osiris Therapeutics, Inc. announced positive results from a 32 patient Phase II study using PROCHYMAL for the treatment of acute Graft vs. Host Disease or GVHD. In the study, 29 of 31, or 94% of evaluable patients responded after receiving two infusions of PROCHYMAL. More significantly, 23 patients, or 74% achieved a complete response, meaning the patients had experienced total clinical resolution of the disease. Currently, PROCHYMAL is being evaluated in a Phase III trial for the treatment of steroid refractory GVHD.

The trial was a randomized, prospective, open label trial, conducted at 16 leading cancer centers within the US. In addition to standard care including steroids, patients were given two infusions of PROCHYMAL three days apart at the onset of moderate to severe (grades II-IV) GVHD. Patients were divided into two groups and received either low dose (2 million cells per kilogram) or high dose (8 million cells per kilogram) of PROCHYMAL. Endpoints of the study included response of GVHD to treatment with PROCHYMAL and the safety and tolerability of the drug at the two different dose levels.

Targacept Announces Positive Results of Phase II Clinical Trial in Major Depression
Targacept, Inc. reported positive results from a double blind, placebo controlled Phase II clinical trial of mecamylamine hydrochloride as an augmentation treatment for major depression. The trial (n=184) evaluated the effects of mecamylamine taken with citalopram hydrobromide, a treatment combination known as TRIDMAC, in patients who did not respond adequately to citalopram alone. Citalopram hydrobromide is a commonly prescribed treatment for depression marketed as Celexa® in the United States.

On one of two primary endpoints in the trial, patients receiving TRIDMAC showed greater improvement on symptoms of depression, as measured by group mean change from baseline on the Hamilton Depression Rating Scale (HAM-D), than patients receiving placebo with continued citalopram therapy. This result was statistically significant on an intent to treat basis (p=0.041) and showed a strong trend on a per protocol basis (p=0.059). HAM-D is a commonly used 17-item scale that evaluates depressed mood and other symptoms of depression and anxiety. The result on the trial's other primary endpoint, achievement of remission, favored the TRIDMAC group over the placebo group, although this result did not reach statistical significance. In addition, the trial included five other rating scales as secondary measures. The results on all five rating scales favored the TRIDMAC group over the placebo group with statistical significance (p<0.05) on a per protocol basis. On an intent to treat basis, the results on three of the five rating scales were statistically significant.

Drug Pipeline Series: Phase I, Nov 6 - Nov 13, 2006

2006-11-14T08:10:00.000-08:00

Neurogen Announces Phase I Clinical Trial for Proprietary Obesity Drug
Neurogen Corporation announced that it has commenced Phase I human testing of the Company's leading drug candidate for treatment of obesity. The compound, NGD-4715, works as an antagonist at the melanin concentrating hormone receptor-1 (MCH1). NGD-4715 and other compounds in the Company's obesity program are wholly-owned by Neurogen.

The Phase I clinical trial is a randomized, double-blind, placebo-controlled evaluation in healthy overweight and obese subjects of the safety, pharmacokinetics, and pharmacodynamics of single rising oral doses of NGD-4715. The study has a planned total enrollment of up to 84 male and female subjects. This single center study will be conducted in the U.S. and standard safety assessments will be made.

Neose Technologies Announces Initiation of Phase I Trial of GlycoPEG-GCSF
Neose Technologies, Inc. announced that its partner, BioGeneriX AG, a company of the ratiopharm Group, has begun dosing healthy volunteers in a Phase I clinical trial of GlycoPEG-GCSF, a long-acting, GlycoPEGylated™ granulocyte colony stimulating factor for the treatment of neutropenia. The trial, which is being conducted in Western Europe, will evaluate the safety, pharmacokinetics and pharmacodynamics of GlycoPEG-GCSF versus Neulasta® in approximately 60 healthy volunteers. The Phase I trial is designed as a single-blind, randomized, ascending-dose study that will evaluate subcutaneous administration of GlycoPEG-GCSF.

G-CSF is prescribed to stimulate the production of neutrophils, and is approved for sale in major markets around the world for the treatment of neutropenia associated with myelosuppressive chemotherapy. Worldwide sales in the G-CSF category were approximately $4 billion in 2005.

Neutropenia is a severe reduction in the number of neutrophils (mature white blood cells) in the circulating blood, commonly associated with cancer chemotherapy. Patients with neutropenia are at increased risk of developing serious infection. If not treated promptly, neutropenia can be life-threatening.

Interferon Alpha Enters Phase Ia Clinical Trial
Maxygen, Inc. announced that Roche has initiated a Phase Ia clinical trial in New Zealand to evaluate the safety, tolerability, pharmacokinetic and pharmacodynamic profile of Maxy-alpha, a next-generation interferon alpha for the treatment of hepatitis C virus infection.

The Phase Ia clinical trial is a double-blind, dose-escalation, controlled study of a single sub-cutaneous administration of Maxy-alpha in healthy volunteers with both placebo and PEGASYS® (peginterferon alfa-2a (40KD)) control groups. Maxy-alpha, also known as R7025, Roche's internal designation for the molecule, is a novel PEGylated interferon alpha variant created through the use of Maxygen's proprietary MolecularBreeding™ directed molecular evolution technologies. Maxy-alpha has been designed to have more anti-viral activity against the hepatitis C virus and be more effective in stimulating immune responses to help combat the infection.

Phase 1 Clinical Trial Results for QUADRAMET® Combination Study in High-Risk Prostate Cancer Patients
Cytogen Corporation announced results from a Phase 1 clinical trial of QUADRAMET® (samarium Sm-153 lexidronam injection) in combination with hormonal therapy and external beam radiation therapy in high-risk, clinically non-metastatic prostate cancer patients. Data from the study indicate that the combination regimen was well tolerated with preliminary anti-tumor activity observed as evidenced by prostate specific antigen or PSA responses.

Twenty patients with newly diagnosed high risk (PSA>20 ng/mL and Gleason score greater than or equal to 7; or greater than or equal to T2 and Gleason score greater than or equal to 8) clinically non-metastatic (known as M0) prostate cancer were treated with a regimen consisting of one month of hormonal therapy followed by a single administration of QUADRAMET followed by four more months of hormonal therapy in combination with external beam radiation therapy (RT). RT was administered as 46.8 Gy to the pelvic region and 23.4 Gy to the prostate (total dose of 70.2 Gy). QUADRAMET was administered in escalation doses of 0.25 mCi/kg (4 patients), 0.5 mCi/kg (4 patients), 0.75 mCi/kg (6 patients) and 1.0 mCi/kg (6 patients). The primary endpoint of the study was assessment of the incidence of Grade 3 (or higher) toxicity following all therapy.

ArQule Announces Data from Phase 1B Trial with ARQ 501 and Docetaxel
ArQule, Inc. announced data from a Phase 1b combination therapy trial with ARQ 501 and docetaxel that support previously announced findings demonstrating clinical tolerability and promising signs of anti-tumor activity in cancer patients with a range of advanced solid tumors who had failed prior treatments with a range of anti-cancer therapies.

These data were presented as a poster at the 18th EORTC-NCI-AACR International Conference on Molecular Targets and Cancer Therapeutics in Prague (A Phase 1b Trial of ARQ 501, a Checkpoint Pathway Activator, in Combination with Docetaxel in Patients with Advanced Solid Tumors - Poster Number 387). Initial data from this trial were disclosed in a June 2006 publication in the 2006 Proceedings of the American Society of Clinical Oncology (ASCO).

ZymoGenetics and Serono Report Detailed Positive Results From Atacicept Phase 1b Clinical Trial in Patients With Lupus
ZymoGenetics, Inc. and Serono presented positive results at the American College of Rheumatology (ACR) annual meeting from a Phase 1b study in systemic lupus erythematosus (SLE) patients treated with atacicept. The results showed that atacicept was well tolerated across all dose levels and schedules in the study. In addition, atacicept therapy was associated with clear biologic activity, as shown by dose-dependent reductions in several biologic markers, consistent with atacicept's proposed mechanism of action.

The primary objective of the dose-escalating Phase 1b clinical trial, which included 49 patients with SLE in 6 cohorts, was to determine the safety and tolerability of atacicept administered subcutaneously. Secondary objectives included examining the effects of various dose and schedule regimens on markers of biologic activity and disease activity.

ZymoGenetics and Serono are in dialogue with the FDA regarding the SLE Phase 2 clinical development program. The companies are planning to initiate the trial in SLE in mid-2007.

AMPLIMED PRESENTS DATA ON IMEXON IN ADVANCED SOLID TUMORS
AmpliMed reported final results from the Phase I trial of its lead drug candidate, Amplimexon (imexon for injection), in patients with advanced solid tumors. The results were presented the International Conference on Molecular Targets and Cancer Therapeutics.
Data from the Phase I study show that Amplimexon is well-tolerated and provides objective evidence of antitumor activity. The multicenter study involved 49 patients with a variety of solid tumors including melanoma, pancreatic, ovarian, colon, uterine, lung and prostate cancers. Patients were administered a range of doses from 20 to 1,000 mg/m2 of Amplimexon as a 30-minute infusion daily for five days every two weeks. The maximum tolerated dose (MTD) of this schedule of administration was determined to be 875 mg/m2/day. Pharmacokinetic studies revealed peak blood levels of imexon at the MTD that were well in excess of those shown to have antitumor effects in preclinical testing. Pharmacodynamic studies showed a correlation between a decrease in the plasma levels of cystine, a thiol-containing compound, and blood levels of imexon, providing additional support for the theory that imexon exerts its effects in part by binding thiols in cells and causing increased intracellular antioxidant levels.
Imexon is a cyanoaziridine compound that showed evidence of activity in limited studies in lung cancer, melanoma and breast cancer that were documented in publications in the 1980s. The potential of imexon as a cancer drug was never fully explored, until 1994 when AmpliMed initiated a program to decipher Amplimexon's mechanism of action. This led to the start in 2003 of a Phase I clinical study of the drug as a standalone therapy in late-stage cancer patients. Further preclinical research revealed that the combined use of Amplimexon and certain other chemotherapeutics resulted in a significant increase in efficacy compared with either drug alone. These findings are now being translated into a series of Phase I/II clinical studies of combination therapy in patients with various types of cancer.

First Patient Enrolled in OXiGENE's Phase Ib Trial of its Lead Vascular Disrupting Agent, CA4P, in Combination with an Antiangiogenic Agent, Bevacizumab (Avastin) for the Treatment of Advanced Cancer
OXiGENE, Inc. announced that the first patient has been enrolled and dosed in its Phase Ib clinical trial in advanced solid tumors, which combines its lead Vascular Disrupting Agent (VDA), CA4P, with an antiangiogenic agent, bevacizumab (Avastin). In a recent Science (Shaked, et al, 2006) publication, the combination of a VDA with an antiangiogenic agent was described as offering a powerful and highly targeted regimen for suppressing tumor growth. Dr. Richard Chin, President and CEO of OXiGENE, stated, "We are very excited to begin enrollment in this important trial. We believe that the combination of CA4P and Avastin has the potential to bring significant benefit to patients. This patient enrollment also highlights our renewed focus on executing our programs rapidly and on schedule." OXiGENE believes that this dose escalation trial is the first step toward fully elucidating the efficacy and safety profiles of combining VDAs and antiangiogenic agents in patients.

InSite Vision Announces Initiation of a Phase 1 Safety Trial on AzaSite Plus™InSite Vision Incorporated announced that a Phase 1 (safety) clinical study for AzaSite Plus (ISV-502), a combination antibiotic/corticosteroid, has been initiated. AzaSite Plus, the next product in the AzaSite product franchise, combines azithromycin and dexamethasone in DuraSite which is InSite Vision's drug delivery system for topical ophthalmic indications.

AzaSite Plus provides the broad bacteria coverage of InSite Vision's AzaSite product (for which an NDA has been filed), featuring reduced dosing and drug safety, while the addition of dexamethasone provides a proven steroid for the treatment of ocular inflammation. The product would be indicated for ocular treatment where inflammation and bacterial infection are present, typically represented in conditions such as blepharitis. The Phase 1 clinical study is intended to evaluate both the safety and tolerability of the AzaSite Plus formulation in normal volunteers.

Drug Pipeline Series: Approvals, Oct. 31 - Nov 6, 2006

2006-11-09T12:30:00.000-08:00

BioMarin Announces Marketing Approval for Aldurazyme in Japan
BioMarin Pharmaceutical Inc. announced that Japan's Ministry of Health, Labor, and Welfare (MHLW) has granted marketing authorization for Aldurazyme® (laronidase), the first specific treatment approved in Japan for patients with the genetic disease mucopolysaccharidosis I (MPS I). Aldurazyme was approved in Japan as an orphan drug.

MPS I is a progressive, debilitating and fatal genetic disease caused by a deficiency of the enzyme alpha-L-iduronidase. This deficiency leads to the accumulation of complex carbohydrates in the lysosomes of cells, leading to the progressive dysfunction of cellular, tissue and organ systems. Resulting symptoms, which span a spectrum of severity, can include impaired cardiac and pulmonary function, delayed physical development, skeletal and joint deformities, reduced endurance, and in some cases, delayed mental function. A majority of patients die before adulthood from complications of the disease.
About Aldurazyme

Aldurazyme® (laronidase) is indicated in the United States for patients with Hurler and Hurler-Scheie forms of MPS I and for patients with the Scheie form who have moderate to severe symptoms. The risks and benefits of treating mildly affected patients with the Scheie form have not been established. Aldurazyme has been shown to improve pulmonary function and walking capacity. Aldurazyme has not been evaluated for effects on central nervous system manifestations of the disorder.

NovaDel Pharma Receives FDA Approval of NitroMist™NovaDel Pharma Inc. announced that NitroMist™ (Nitroglycerin Lingual Aerosol) has been approved by the U.S. Food and Drug Administration (FDA) for acute relief of an attack or acute prophylaxis of angina pectoris due to coronary artery disease. NitroMist™ is NovaDel's first product approval utilizing its proprietary oral spray technology. The North American commercial rights for NitroMist have been licensed to Par Pharmaceutical Companies, Inc. (NYSE: PRX).

Data from the NitroMist™ clinical trials demonstrate the drug's efficacy in the treatment of angina. In a double-blind, single-center, placebo-controlled, 4-period crossover study in 30 subjects with stable angina pectoris, doses of 0.2, 0.4, and 0.8 mg of nitroglycerin delivered by NitroMist™ were compared to placebo. The primary efficacy endpoint was exercise tolerance as measured by time to development of moderate angina while on an exercise treadmill. The primary endpoint was achieved with all three nitroglycerin oral spray groups demonstrating statistically significantly increase in time to angina compared to placebo (p less than or equal to 0.0003).

Drug Pipeline Series: Submissions, Oct 31 - Nov 6, 2006

2006-11-09T12:27:00.000-08:00

Tercica Reports Somatuline® Autogel® NDA for Acromegaly Submitted to FDA

Tercica, Inc. reported that earlier this week its partner IPSEN submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for Somatuline® Autogel® (lanreotide acetate) injection 60, 90 and 120 mg to treat patients with acromegaly. Tercica licensed from Ipsen the rights to develop and market Somatuline® Autogel® in the United States and Canada in a transaction that closed on October 13, 2006.
The FDA will determine within 60 days whether the submission will be accepted for filing.
As of December 31, 2005, Somatuline® and Somatuline® Autogel® had marketing authorizations in over 50 countries for the treatment of acromegaly and neuroendocrine tumors. The product is supplied in pre-filled syringes to be injected subcutaneously for easier administration than other long acting somatostatin analogues.

Somatuline® Autogel® is an injectable sustained-release formulation containing lanreotide, a somatostatin analogue. Somatuline® was initially developed in Europe for the treatment of acromegaly (a disorder caused by the over-production of growth hormone secondary to a benign tumor of the anterior pituitary gland) and, in most European countries, is also approved for the treatment of symptoms associated with neuroendocrine tumors. The Somatuline® Autogel® formulation requires no excipient other than water and releases lanreotide over a period of at least 28 days and up to 56 days. The product is conditioned in a pre-filled syringe for easier administration than other long-acting somatostatin analogue. In acromegaly, Somatuline® is used primarily when circulating levels of growth hormone remain high despite surgery or radiotherapy, and through its inhibitory effects, Somatuline® lowers growth hormone and IGF-1 levels, thus controlling disease progression and relieving the symptoms associated with active disease.

Drug Pipeline Series: Phase III, Oct 31 - Nov 6, 2006

2006-11-09T12:25:00.000-08:00

SCHWARZ REPORTS POSITIVE RESULTS FROM EPILEPSY TRIAL
Schwarz Pharma has announced that results from the second Phase III trial with oral lacosamide for adjunctive therapy of epilepsy are clinically relevant and statistically significant in both primary variables, reduction of seizure frequency and a 50 percent responder rate.
This multicenter, double-blind, placebo-controlled clinical trial, performed in the United States, included a titration phase of six weeks and a maintenance phase of 12 weeks. A total of 405 patients with uncontrolled partial seizures were randomized to treatment with adjunctive placebo or 400- or 600-mg lacosamide divided into two doses per day. The primary variables were reduction of seizure frequency and a 50 percent response to treatment.
Both the 400- and 600-mg/day lacosamide treatment groups were statistically significantly over placebo in reducing seizure frequency from baseline to maintenance. Statistical significance was also observed for both lacosamide doses in the statistical analysis of responders. Lacosamide demonstrated an adverse events profile generally expected with CNS drugs.

Drug Pipeline Series: Phase II, Oct 31 - Nov 6, 2006

2006-11-09T12:18:00.000-08:00

Palatin Technologies and King Pharmaceuticals Report Results For Two Phase 2B Clinical Trials Evaluating Bremelanotide in Male Erectile Dysfunction Patients
Palatin Technologies, Inc. and King Pharmaceuticals, Inc. announced positive results from two Phase 2B trials evaluating bremelanotide for the treatment of male erectile dysfunction (ED). The two Phase 2B clinical trials were double-blind, placebo-controlled, parallel dose trials that included a one month run-in period and a three-month treatment period.

The primary efficacy endpoint for both trials was the change in the Erectile Function domain of the International Index of Erectile Function (IIEF-ED) from baseline to the end of the three-month treatment period. Study 16 was a clinical trial evaluating the safety and efficacy of bremelanotide in 726 non-diabetic patients with mild to severe ED. Study 17 similarly evaluated 294 patients with ED and diabetes mellitus. The primary objective of the studies was to characterize the efficacy and safety of bremelanotide in these two ED populations and to identify the dose(s) to use in further development. Data from these and other studies will be the basis for discussions with the U.S. Food and Drug Administration (FDA) at an end-of- Phase 2 meeting.

EntreMed Commences Phase 2 Clinical Trial With Panzem® NCD in Ovarian Cancer
EntreMed, Inc. announced commencement of a multi-center, Phase 2 clinical trial with its clinical-stage drug candidate, Panzem® NCD (2ME2 or 2-methoxyestradiol), in patients with recurrent or resistant epithelial ovarian cancer. The study will be conducted by the Hoosier Oncology Group, headquartered in Indianapolis.

Primary objectives for this single-agent Phase 2 study will be to assess the safety, pharmacokinetics, tumor response rate, and progression-free survival (PFS) in ovarian cancer patients receiving orally-administered Panzem® NCD. Patients with recurrent or resistant epithelial ovarian cancer will be treated. EntreMed received orphan drug designation for 2ME2 from the FDA for treatment of ovarian cancer.

Hana Biosciences Initiates Phase II Trial of Talvesta (talotrexin) for Injection in Acute Lymphoblastic Leukemia
Hana Biosciences announced the initiation of a multicenter Phase II clinical trial with Talvesta™ (talotrexin) for Injection in adult patients with relapsed or refractory acute lymphoblastic leukemia (ALL).

The primary objective of this Phase II portion of an ongoing Phase I/II open-label study is to evaluate the complete remission rate (CR/CRp) of Talvesta in relapsed or refractory ALL patients. Secondary objectives are to evaluate the safety and tolerability of Talvesta in this setting as well as duration of complete remission and overall survival. Data from the Phase I portion of this clinical trial will be presented during the 48th Annual American Society of Hematology (ASH) Meeting in December in Orlando, Florida, on Sunday, December 10th.

Novacea Initiates Phase 1/2 Trial of AQ4N in Glioblastoma Multiforme
Novacea, Inc. announced that it has initiated a multicenter,Phase1b/2a open-label clinical trial of AQ4N (banoxantrone), in combination with radiotherapy and temozolomide, for safety, tolerability and activity in patients with newly diagnosed glioblastoma multiforme (GBM).

The trial consists of two parts. The primary objective of the first part will be to evaluate safety and tolerability of three dose levels (200 mg/m2, 450 mg/m2and 750 mg/m2). The second part will further evaluate safety and tolerability as well as efficacy and the highest safe and tolerated dose of the AQ4N treatment determined in part one. Novacea expects to enroll approximately 60 patients in the trial.

CombinatoRx Drug Candidate CRx-102 Demonstrates Positive Phase 2 Results in Rheumatoid Arthritis
CombinatoRx, Incorporated announced positive results of its randomized, blinded, placebo-controlled phase 2 clinical trial of CRx-102 in rheumatoid arthritis (RA). The trial compared CRx-102 plus a disease-modifying anti-rheumatic drug (DMARD) to placebo plus DMARD (control) in subjects with RA. In this trial, CRx-102 demonstrated statistically significant improvements on primary and secondary endpoints.

CRx-102 is an oral synergistic combination drug candidate containing the cardiovascular agent dipyridamole and an unconventionally low dose (3mg) of the steroid prednisolone. CRx-102 works through a novel mechanism of action in which dipyridamole selectively amplifies prednisolone's anti-inflammatory and immunomodulatory activities without replicating its side effects.

CRx-102 was generally well tolerated and there were no serious adverse events reported for subjects treated with CRx-102. The most common adverse events observed with CRx-102 that occurred with a frequency of greater than 5% were headache, gastro-intestinal symptoms and dizziness, known side effects of dipyridamole, one of the two components of CRx-102.

Opexa Begins Dosing Patients in Phase IIb Trial of Tovaxin™ for Multiple Sclerosis
Opexa Therapeutics, Inc. announced that it has dosed the first patient in its 150-patient Phase IIb clinical trial of Tovaxin™ in multiple sclerosis. Enrollment is expected to be completed by mid-2007. There are currently 31 trial sites in the U.S., all of which are actively recruiting patients; the first patient was treated by Dr. Suzanne Gazda, Principal Investigator at Integra Clinical Research in San Antonio, Texas.

As previously announced, this Phase IIb clinical study will include 150 patients in a multicenter, randomized, double blind, placebo-controlled trial designed primarily to evaluate the efficacy, safety and tolerability of the Tovaxin T Cell vaccination with clinically isolated syndrome (CIS) and relapsing-remitting MS (RR-MS) patients. A total of 100 patients will receive Tovaxin, while 50 will receive placebo. The study is designed as a two-arm, 52-week, parallel-group study, whereby patients will be given five subcutaneous injections at 0, 4, 8, 12 and 24 weeks. The analyses will be performed at the end of the 52-week study to assess the safety and efficacy of Tovaxin. The primary efficacy variable is the cumulative number of gadolinium-enhancing lesions on T1-weighted MRI scans summed over the Week 28, 36, 44, and 52 MRIs. The secondary efficacy variables are the cumulative number of new gadolinium-enhancing lesions at Weeks 28-52, the change in T2-weighted lesion volume, and the annualized relapse rate.

Neurogen Announces Start of Phase II Proof-of-Concept Trial for Investigational Pain Drug
Neurogen Corporation announced that Merck & Co. Inc., through an affiliate, has begun a Phase II proof-of-concept clinical trial to study MK-2295 (NGD-8243) for the treatment of post-operative dental pain. MK-2295 is one of several drug candidates Merck is developing as part of its exclusive worldwide alliance with Neurogen to develop oral medicines targeting the VR1 receptor.

The initiation of the Phase II study triggers a $3 million milestone payment from Merck to Neurogen. Through the alliance, Neurogen and Merck have generated a broad spectrum of chemical intellectual property and several leading drug candidates, including MK-2295. The companies will select the most promising of the lead candidates for further development once proof-of-concept has been established.

The Phase II proof-of-concept trial is a randomized, double-blind, placebo controlled study, designed to determine the efficacy of MK-2295 in the treatment of post-operative dental pain. In single ascending dose Phase I trials conducted to date, MK-2295 was potent and active at the VR1 target and generally well tolerated with no serious adverse events. Multiple ascending dose studies are ongoing.

PTC Therapeutics Announces Positive Phase 2 Results For PTC124 in Cystic Fibrosis
PTC Therapeutics, Inc. announced the findings from two Phase 2 clinical trials of PTC124 in patients with cystic fibrosis (CF) due to a nonsense mutation. The results suggest that PTC124 can restore function of the cystic fibrosis transmembrane conductance regulator (CFTR) protein in airway cells and significantly reduce blood neutrophil counts that are a hallmark of the CF disease process.
The initial data were presented at the North American Cystic Fibrosis Conference in Denver, Colorado.

PTC sponsored a multi-site, open-label, dose-ranging Phase 2 clinical trial program to determine whether PTC124 can induce production of active CFTR protein. Identical studies in the U.S. and Israel evaluated nasal transepithelial potential difference (TEPD) as a surrogate for CFTR protein production. A change in CFTR-mediated chloride transport toward normal during PTC124 treatment would suggest that PTC124 is inducing the cells to make full- length, functional CFTR protein.

Drug Pipeline Series: Phase I, Oct 31- Nov 6, 2006

2006-11-09T11:49:00.000-08:00

TARGEGEN INITIATES STUDY OF TOPICAL AMD DRUG

TargeGen has begun a single-site Phase I clinical trial involving TG100801, a small-molecule, topically applied, multitargeted kinase inhibitor for the treatment of age-related macular degeneration (AMD) and other debilitating diseases of the eye. The trial, involving approximately 45 subjects, is expected to be completed by the end of the first quarter of 2007. The company hopes to initiate Phase II studies with TG100801 in mid-2007.
TG100801, applied daily in eyedrop form, is designed to suppress disease-related edema, angiogenesis and inflammation. Edema, angiogenesis and inflammation are pathological hallmarks of macular degeneration, diabetic macular edema and proliferative diabetic retinopathy. Currently approved therapies for macular degeneration require repeated injection into the eye and typically act on only VEGF-mediated retinal leakage.
TargeGen believes that TG100801 may offer equal or superior efficacy to injectable agents, while offering patients the greater convenience and potential safety advantages of noninvasive delivery. In published preclinical studies conducted by outside retinal disease experts, TG100801 demonstrated the ability to reduce VEGF-mediated retinal leakage, angiogenesis and inflammation after topical instillation. TG100801 is the second internally discovered TargeGen compound to enter clinical trials.

MACUSIGHT INITIATES WET AMD STUDY

MacuSight has begun a Phase I study of its lead product candidate in patients with wet age-related macular degeneration (AMD). This trial, which will enroll a total of 30 patients, is designed to evaluate the safety and tolerability of MacuSight's proprietary formulation of sirolimus (rapamycin) when administered in various doses through two different types of ocular injections.
Investigators for this randomized, open-label, dose-escalation study will treat patients with a single subconjunctival (just under the lining layer over the white of the eye) or intravitreal (into the back of the eye) injection of MacuSight's sirolimus formulation. The trial will include six treatment arms with patients receiving one of three doses of sirolimus via subconjunctival injection or one of three doses of sirolimus via intravitreal injection. Each administration of sirolimus will provide the patient with exposure to the compound for up to approximately three months.
Sirolimus, originally known as rapamycin, is a highly potent, broad-acting compound that has demonstrated the ability to combat disease through multiple mechanisms of action including immunosuppressive, anti-angiogenic, anti-migratory, anti-proliferative, anti-fibrotic and anti-permeability activity. Based on the versatility associated with these multiple mechanisms of action, MacuSight believes that its sirolimus product may serve as a highly efficacious therapeutic for a wide range of ocular diseases and conditions, including the treatment and prevention of wet AMD, as well as the treatment of diabetic macular edema (DME). The company recently initiated a similar Phase I trial in patients with DME.

Adolor Falls; FDA Requests More Data On Lead Drug

2006-11-06T13:22:00.000-08:00

Shares of Adolor Corp. (ADLR) fell to an all-time low Monday after the U.S. Food and Drug Administration requested additional safety data for the company's lead candidate drug, Entereg.

First Albany Capital lowered its rating for the therapeutic-based biopharmaceutical company to neutral from strong buy, saying the FDA request implies substantial delay to market "or worse."

In the second so-called approvable letter from the FDA, the agency requested 12-month safety data, including an analysis of any serious cardiovascular events, from an ongoing study of Entereg, or alvimopan, as a treatment for opioid-induced bowel dysfunction in patients with chronic noncancer pain. Such a letter typically means a drug might ultimately get approved, but only after the FDA reviews more data.

"Our reaction is that the FDA, clearly not considering Entereg a medical breakthrough, is concerned about extended off-label use in chronic-pain patients," First Albany analyst David Webber said in a note. First Albany makes a market in Adolor shares. Webber doesn't own any shares in the company.

Adolor shares recently changed hands at $7.91, down $6.03, or 43.3%, on about 14 times the average daily volume. Earlier Monday, the stock dipped to $7.63, an all-time low for Adolor, which went public in November 2000. The previous bottom was set February 2005 at $7.97 a share.

Some analysts had expected FDA approval for Entereg, despite mixed clinical-trial results across five Phase III studies.

Adolor and its partner, GlaxoSmithKline PLC (GSK), said Sept. 5 that the drug did not achieve statistical significance in the studies, though both companies also said they would continue to investigate the data.

Sibiono Genetech Uses Gene Therapy To Treat Cancer

2006-11-06T13:20:00.000-08:00

This year's winners occupies a sensitive area of health: gene therapy. Gene therapy, put simply, is when genes -- the instruction manual for how everything in an organism operates -- are manipulated to alter the way a cell -- the components of the organism -- works. It's called therapy because it has been developed to tackle disorders arising from human genes that have mutated or are defective.

This is a sensitive area for several reasons: gene therapy is as controversial as any area of study involving our genetic material. And the death of a patient in the U.S. in 1999 has cast a long cloud over researchers and investors. Which is partly why the first company to commercialize gene therapy for cancer is based in China: Shenzhen-based SiBiono GeneTech Co.

Gene therapy works like this: Genes contain the information necessary for cells to function and multiply. This genetic information is contained in DNA, long thin strands built from combinations of four sorts of bases.

When cells multiply by splitting, these combinations are passed on and checked by genes called regulators for errors, so that new cells are identical to the old cells.

But the process can sometimes go wrong, creating mutant cells. Or sometimes we are born with defective genes. Either way, gene therapy's approach is to replace the bad gene with a good one.

It sounds simple enough, but it's not. The first problem is to identify the healing, or therapeutic gene. Then, a way has to be found to deliver the corrected gene to the target cells, because a gene, unlike chemicals, cannot spontaneously enter cells.

This is usually done, perhaps illogically, by giving the patient a virus. A virus, it turns out, is a very good delivery system for this kind of thing since it's good at getting inside cells and then duplicating (the virus is modified so it is not pathogenic, or disease causing, and won't replicate once inside host cells.)

Once the gene is in the cell, it still has a long way to go. First it must find its way into the inner sanctum of the cell, the nucleus. From there it must be activated so that it can start issuing its payload to the cell.

In the case of cancer, gene therapy largely focuses on one small gene -- p53, so called because its expressed protein has a molecular weight of 53,000 daltons (a dalton is roughly the weight of a hydrogen atom).

The p53 gene is a very special, very complex gene, since it appears to act as a kind of guardian to the genome, or central directory of genes. The p53 is still only partially understood, but one thing is clear: it's intimately connected to at least half of all human cancers.

A group of special proteins constantly patrol the genome looking for faults in the DNA; if they find one they immediately report to the p53 gene, which in turn is released in packs of four to sort out the problem.

"DNA damage," David Lane, who discovered p53 in 1979, wrote in the New Scientist, "makes the genome unstable and prone to mutation and disintegration."

The problem is that DNA is constantly being multiplied as cells divide, so the damage needs to be resolved quickly before it spreads.

This is what p53 genes do, putting a halt on cell growth until repairs are done. If the cell is beyond repair, the p53 gene forces the cell to self-destruct, something called apoptosis.

But what happens if the p53 isn't working properly? This is what happens in many cancer cases. If the p53 gene is faulty, or has been bent out of shape by a virus, the patrolling proteins may report back on faults in the DNA chain, but the p53 gene does not function correctly.

In this case there is nothing to stop the cancerous cells from multiplying, and tumors to grow. "For a healthy person cells just divide regularly, via a regulator gene like p53," says Dr. Chiushi Fu, assistant to the founder and CEO of SiBiono, Dr. Zhaohui Peng. "But with a cancer patient the regulatory cell loses control so the cells divide without limit."

The secret, then, in combating cancer with gene therapy is to somehow ensure the p53 does its job. The most obvious way is to introduce "good" p53 genes into tumor cells, which is exactly what SiBiono GeneTech does by building a payload of a "healthy" p53 gene packed into a viral delivery mechanism called an adenoviral vector, containing a class of virus that would normally cause respiratory, intestinal and eye infections (including the common cold).

Once inside the nucleus the particles will unload their healthy p53 genes which, it is hoped, will then begin to do the job they're supposed to do -- halting the spread of cancerous cells.

SiBiono, under Dr. Peng, saw cancer as a natural focus for gene therapy. Unlike surgery, chemotherapy or radiotherapy, gene therapy went to the heart of the problem by tackling the genetic abnormality that causes the cancer in the first place.

The Gendicine therapy, the company's submission for the award says, "treats cancer from the very root of its initiation and development." That's not to say gene therapy can't be conducted in tandem with other therapies.

Indeed, SiBiono says that trials have thrown up some unexpected but positive findings in patients, including improved appetite, relief of cancerous pain and resistance to the side effects caused by radiotherapy or chemotherapy.

SiBiono has also been fortunate, if that's the right word, to step into a void left by setbacks in Europe and the U.S.

In 1999 an 18-year-old American man died from multiple organ failure four days after joining a gene-therapy trial, apparently reacting to the adenovirus carrier. And U.S. authorities in 2003 placed a temporary halt on some gene-therapy trials using a different viral-delivery mechanism after a French child developed leukemia-like conditions after gene therapy.

China, on the other hand, has been supportive of work in this field, including government investment from ministries and the local municipal government.

The company denies that processes are more lax, pointing out that China's regulatory body issued gene-therapy guidelines in 2003. Clinical costs are also lower in China, a fraction of the tens of thousands of dollars a U.S. company would have to pay per person.

Gendicine was approved by China's regulatory body in October 2003 and was officially launched six months later, the world's first commercially available gene-therapy product.

More than 4,000 patients from 26 countries have received treatment, without any reports of severe side effects, according to the company. SiBiono says sales of Gendicine reached 11.4 million renminbi ($1.4 million) in 2004 and it projects sales this year of nearly 19 million renminbi.

But that's not to say it has been a simple process to get this far. In the early years "it was a very difficult road," says Dr. Fu. "We put a lot of money in and at that time there was still risk."

Western competitors had more money, and trying to recruit patients in China was not easy. "We had to tell them what it is, they had no idea -- including the doctors," Dr. Fu recalls.

In the end, says Dr. Fu, the continued success of Gendicine will depend on whether it continues its initial promise. "The efficacy of the drug is the bottom line," he says. "Or I should call it the lifeline?"

Sudden Infant Death Syndrome Tied To Faulty Arousal System

2006-11-06T13:19:00.000-08:00

Babies who die of sudden infant death syndrome have abnormalities in the part of the brain that helps control functions like breathing, blood pressure and arousal, says a study being published in Wednesday's issue of the Journal of the American Medical Association.

The syndrome, known as SIDS, involves the sudden and unexplained death of an infant under one year of age. Typically, a baby is found dead after having been put to sleep and shows no sign of having suffered. Although studies have identified risk factors for SIDS, such as putting infants to bed on their stomachs, there has been little understanding of the syndrome's biological causes.

According to the National Institutes of Health, which funded the study, the new finding is the strongest evidence to date suggesting that innate differences in a specific part of the brain may place some at increased risk for the syndrome. To reach that conclusion, researchers examined the brains of 31 babies who had died of SIDS and 10 who had died from other causes.

They found that abnormalities in the brain stem appear to affect the ability to use and recycle a chemical called serotonin, which is responsible for regulating mood as well as vital body functions.

When babies sleep face-down or have their faces covered by bedding, they are thought to breathe in the just-exhaled carbon dioxide, therefore taking in less oxygen. Normally, the rise in carbon dioxide activates nerve cells in the brain stem that stimulate respiratory and arousal centers in the brain. A normal baby would wake up, turn over and start breathing faster, but one with a defective serotonin system wouldn't receive the warning signals.

"The findings show that SIDS is not a mysterious occurrence that happens and nobody really knows why," said the lead author of the study, Dr. David Paterson, of the Children's Hospital Boston and Harvard Medical School.

He said this conclusion is important, particularly for parents who often blame themselves for the infant's death.

"This data here is something that really says 'No, (parents) didn't do anything to cause this.' This is a disease and they are not responsible for the disease."

Paterson, however, said results from the study suggest that known risks for SIDS contribute to the deaths. About 48% of the SIDS victims in the study were found sleeping on their stomachs, while 29% were found face down and 23% were sharing a bed at the time of death.

According to the researchers, the results also help explain why the syndrome occurs twice as often in males than females, as male SIDS victims studied had smaller numbers of a type of serotonin receptor than did female SIDS babies.

Paterson said the next step is to develop a diagnostic test to identify infants at risk for the syndrome.

He acknowledged, however, that treatment is far from becoming a reality because it isn't yet known what kind of defect is present in the serotonin system of those who die of the syndrome, and even whether they produce more or less of the chemical than normal.

Antidepressants such as Prozac address serotonin imbalances, but Paterson said "it is far too early to say that it will be something like Prozac that we would use, because we don't really know what is going on."

In the meantime, the study suggested that "prenatal insults" like smoking and alcohol use may influence the development of the serotonin system in babies, and that parents should follow all guidelines available to ensure they are raised in a healthy environment.

SIDS is the leading cause of death in U.S. infants after the newborn period, affecting one out of every 1,500 live-born babies.

Pfizer Cholesterol Drug Increased Blood Pressure

2006-11-06T13:17:00.000-08:00

Pfizer Inc. (PFE) said preliminary results from its Phase III trial of torcetrapib and Lipitor showed a 56% increase in HDL cholesterol and a 27% decrease in LDL cholesterol, but also an increase in blood pressure greater than that in previous studies.

However, analysts said that, while the increase in blood pressure should be examined, torcetrapib and Lipitor have potential to be very effective together.

Pfizer shares were recently down 74 cents, or 2.7%, at $26.47, on volume of 53 million shares, compared with average daily volume of 28 million.

According to an analyst note from Chris Schott of Banc of America Securities LLC, while "the mix of data confirms our belief that Pfizer has a potentially very efficacious product on their hands," morbidity and mortality data will probably be necessary for the product to be approved. Those data are expected in 2007.

Associates of Banc of America hold shares of Pfizer.

The drug company said patients in the group showed an average increase in systolic blood pressure that was about one millimeter of mercury above the two-to-three millimeter range observed in Phase II studies.

Pfizer said it doesn't believe this will alter the "favorable clinical profile" of torcetrapib and Lipitor to treat cardiovascular disease.

In a note, analyst James Kelly of Goldman Sachs & Co. (GS) said "we believe that these data are concerning, but must be put into context." He said without baseline blood pressure levels, "it's not known if the higher blood pressure is clinically relevant."

Goldman Sachs said the analyst, a member of his team or a member of the research analyst's household has a financial interest in Pfizer.

Analyst Timothy Anderson of Prudential Equity Group LLC said "directionally, this slight increase in blood pressure is negative, but at the end of the day we don't think it changes the equation: It will continue to come down to how robust the efficacy data is from the two sets of ultrasound trials Pfizer is running," to be reported in March.

Pfizer cautioned the studies are "far from complete," adding the early results cover less than 25% of all the patients in the entire clinical program. It said no final conclusions on the efficacy and safety of torcetrapib/atorvastatin can be drawn until the lipid and imaging studies, and the accompanying statistical analysis, are completed.

Emisphere Oral Insulin Shown Safe,But Shares Drop

2006-11-06T13:16:00.000-08:00

Emisphere Technologies Inc. said its oral insulin product proved safe and effective among Type II diabetes patients in a trial, but investors were hoping for more definite information and sold off the shares.

Shares of the biopharmaceutical company plunged as much as 27% after the announcement. The stock rebounded recently to trade 11% lower, at $7.92 a share, with 5.9 million shares traded - more than 17 times the daily average.

Volatility in the trading of the company's stock has been exacerbated the large number of shares sold short.

Investors who "short" shares borrow them and sell them, betting the price will fall and they will be able to buy the shares back later at a lower price for return to the lender. In general, the higher the short interest, the more investors expect a downturn. Short positions rise in value as stocks fall, and vice versa.

As of Oct. 13, approximately 28% of the company's outstanding shares are sold short, according to the latest figures from Nasdaq. This was 13% rise from the previous month.

Tarrytown, N.Y.-based Emisphere on Monday said the trial was designed to assess the efficacy and safety of low and high doses of oral insulin tablets compared with a placebo among patients with Type II diabetes mellitus.

Emisphere said it recorded no significant adverse events during the study, which paid particular attention to concerns about hypoglycemia or excessively low blood sugar. It said a statistically significant number of patients lowered their Hemoglobin A1c levels, a measure of glucose control, by more than 1.1%, as compared to patients in the placebo group who were receiving a standard treatment.

The company said it observed a dose response for patients with the most debilitating conditions who required the largest doses of the standard metformin treatment.

"The important part to look at is that they saw statistical significance in the population with the most debilitating disease (and) highest doses. That's an important endpoint," said analyst Stephen Brozak of WBB Securities LLC. "But on the other side, the study did not have what some of the shorts were looking for: more news."

Brozak said the Phase II trial answered questions about safety but that the company would now need to focus on studying the effectiveness of different doses among different patient groups at various stages in the disease.

Brozak also pointed out that other novel insulin-delivery methods, such as pulmonary delivery, had suffered setbacks.

"We are very pleased with these study results," Emisphere Chairman and Chief Executive Michael Goldberg said during a conference call with analysts.

Goldberg said the company only recently gained access to the data and had more analyses to conduct. He said during a conference call that the company would now be able to focus on further safety and dosage objectives in future trials.

"What the market might be missing is that with all of this we were able to have a very significant effect," Goldberg said. "There was not a single patient in the placebo arm that had a drop greater than 1.1 [in HbA1c]."

Goldberg said the trial data might encourage doctors with sicker patients, those who could potentially demonstrate the most significant improvement from the oral treatment, to participate in future studies now that the drug had proven to have an effect.

Emisphere said the results also might help it find a major pharmaceutical company with which to partner for the oral treatment, which it hopes will allow patients to avoid frequent glucose monitoring and insulin titration.

Drug Pipeline Series: Approvals Oct23-Oct30, 2006

2006-11-01T08:26:00.000-08:00

FDA Approves New Formulation for NEXIUM
AstraZeneca announced that a new formulation for its prescription proton pump inhibitor NEXIUM ® (esomeprazole magnesium) has been approved by the US Food and Drug Administration (FDA). NEXIUM For Delayed-Release Oral Suspension is now approved for the treatment of GERD, including symptomatic gastroesophageal reflux disease, healing and maintenance of healing of erosive esophagitis (EE), and risk reduction of NSAID-associated gastric (stomach) ulcers.
Each packet of NEXIUM For Delayed-Release Oral Suspension contains either 20 mg or 40 mg of esomeprazole, the same active ingredient used in NEXIUM Delayed-Release Capsules. The esomeprazole granules and inactive granules used in this formulation are mixed with water to form a suspension and are given by oral, nasogastric or gastric administration.
The new formulation of NEXIUM For Delayed-Release Oral Suspension will be available in the first quarter of 2007.

TYZEKA™ (telbivudine) Approved by U.S. Food and Drug Administration (FDA) as a New Treatment for Patients with Chronic Hepatitis B
Idenix Pharmaceuticals, Inc. announced the approval of TYZEKA™ (telbivudine) by the U.S. Food and Drug Administration (FDA) as a new once-a-day oral treatment, taken with or without food, for patients with chronic hepatitis B (CHB). TYZEKA rapidly and profoundly(1) suppresses the hepatitis B virus (HBV) in adult patients with evidence of viral replication and either evidence of persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease.
Data from the pivotal phase III clinical trial, known as the GLOBE study, compared TYZEKA to lamivudine in 1,367 patients. The primary efficacy endpoint of the GLOBE study was therapeutic response at one year, a composite endpoint coupling viral suppression (serum HBV DNA suppression below 100,000 copies/mL) with either improved liver disease markers (ALT normalization) or loss of detectable hepatitis B e-antigen (HBeAg). In HBeAg-positive patients, therapeutic response was 75 percent among patients treated with TYZEKA and 67 percent for those patients treated with lamivudine, while the response for HBeAg-negative patients after one year was 75 percent vs. 77 percent, respectively. In the GLOBE study, patients who achieved non-detectable HBV DNA levels at 24 weeks were more likely to undergo e-antigen seroconversion, achieve undetectable levels of HBV DNA, normalize ALT, and minimize resistance at one year.

FDA APPROVES SCHERING'S BETASERON FOR EARLY STAGE MS
Berlex, a U.S. affiliate of Schering AG, announced that the FDA has expanded the indication of Betaseron (interferon beta-1b) to include patients with multiple sclerosis (MS) who have experienced a first clinical episode and have MRI features consistent with MS. Betaseron is indicated for the treatment of relapsing forms of multiple sclerosis to reduce the frequency of clinical exacerbations. Betaseron is the only high dose, high frequency interferon beta indicated for patients at the earliest stage of MS.
The new indication is based on results from the BENEFIT study in patients with a first clinical demyelinating event and MRI features suggestive of MS. The two-year study showed that treatment with Betaseron delayed the time to a second clinical event by one year compared with placebo. BENEFIT is the only trial to demonstrate the efficacy of a high dose, high frequency interferon beta as an effective treatment for patients with early MS. In addition to establishing efficacy in this group of patients, the study also showed that patients with early MS found Betaseron to be a safe and well-tolerated treatment, as evidenced by the findings that 93 percent of patients completed the study.
Betaseron has more than 17 years of clinical experience, with a well-established safety profile resulting from more than 700,000 patient years of treatment. A long-term follow-up study demonstrated that Betaseron remains consistently safe, effective and well-tolerated over the long term. Results of the study show that long-term continuous use of Betaseron provided 13 years of cane-free mobility, which is, on average, six years longer than when compared with untreated patients from a natural history cohort. The study also showed that patients who continuously used Betaseron experienced a significant delay in progression to secondary progressive multiple sclerosis by 6.6 years compared with patients who were not on continuous Betaseron treatment.

Pharmaxis' ARIdol Gains Swedish Approval
Pharmaceutical company Pharmaxis announced that it has received marketing approval for its asthma diagnostic and management product Aridol in Sweden, a crucial market for gaining wider European approval.
Following the Swedish registration, Pharmaxis will seek marketing of Aridol in the 27 other European Union member states via the mutual recognition procedure. Individual approvals are expected from early next year.
Aridol is Australia's first true molecule-to-market therapeutic product -- discovered, developed, manufactured and marketed over 12 years by wholly Australian interests. The exhaustive clinical trials were generously assisted by Australian Government research grants, including the current P3 Scheme.
A simple-to-use airways inflammation test, Aridol is administered as a dry powder in a hand-held inhaler. It is approved in Sweden to identify patients with asthma, determine the severity of their disease and the effectiveness of their current treatment.

Drug Pipeline Series: Submissions Oct23-Oct30, 2006

2006-11-01T08:25:00.000-08:00

IDM Pharma Submits New Drug Application to the FDA for Junovan™ (mifamurtide) in the Treatment of Osteosarcoma
IDM Pharma announced that the company has submitted an electronic New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for Junovan™ (mifamurtide for injection), requesting approval for its use in the treatment of newly diagnosed resectable high grade osteosarcoma patients following surgical resection in combination with multiple agent chemotherapy.
The Junovan NDA submission includes efficacy and safety data from 678 patients with non-metastatic resectable osteosarcoma, 332 of whom received Junovan, and from 115 patients with metastatic or unresectable osteosarcoma, 39 of whom received Junovan in the controlled Phase III trial conducted by the Pediatric Oncology Group (POG) and the Children's Oncology Group (COG), sponsored by the Division of Cancer Treatment and Diagnosis of the National Cancer Institute (NCI). A summary of the data from the Phase III trial is provided below. The biological effects and safety of Junovan are further supported by data from 17 Phase I and II clinical studies performed by Ciba-Geigy in which an additional 248 patients received at least one dose of Junovan.

Drug Pipeline Series: Phase III Oct23-Oct30, 2006

2006-10-31T13:21:00.000-08:00

NICOX REPORTS RESULTS FROM OSTEOARTHRITIS TRIAL
NicOx has announced results from a successful Phase III trial for naproxcinod (HCT 3012) in patients with osteoarthritis of the knee (the 301 study). Both doses of naproxcinod were shown to be superior to placebo on all three co-primary efficacy endpoints of the study. Blood pressure data for both naproxcinod doses showed a sustained reduction versus baseline and naproxen at all time points, confirming earlier published clinical data. Naproxcinod is the first compound in the COX-inhibiting nitric oxide-donating class.
In terms of the co-primary endpoints of the study, both of the naproxcinod doses (375 and 750 mg) were shown to be superior to placebo, with this being highly statistically significant in terms of the mean change from baseline at week 13 in the following scores: the WOMAC pain subscale, the WOMAC function subscale and patients' overall rating of disease status.
During the trial, patients' blood pressure was measured at each visit. Prespecified analyses of the difference between the blood pressure at baseline and the measurements at week two, six and 13, demonstrated that both naproxcinod 750 and 375 mg decreased systolic and diastolic blood pressure. This effect was sustained until the 13-week time point and clearly differentiated naproxcinod from naproxen.
Naproxcinod also showed good overall safety: 46.7 percent of the patients treated with naproxcinod 750 mg and 40.8 percent on naproxcinod 375 mg experienced at least one adverse event, compared to 56.4 percent on naproxen 500 mg and 38.7 percent on placebo. The number of serious adverse events was low and evenly spread among treatment groups. The number of adverse hypotensive events was low across all groups.

Titan Initiates Phase III Development Program for Probuphine® in the Treatment of Opioid Dependence
Titan Pharmaceuticals, Inc. announced the initiation of a randomized, double-blind, placebo-controlled, multi-center Phase III clinical study of Probuphine in the treatment of opioid dependence. The 150 patient study will evaluate the safety and effectiveness of treatment with Probuphine versus placebo in reducing opioid dependence over 24 weeks of treatment. This study is part of a registration directed program intended to obtain marketing approval of Probuphine for the treatment of opioid addiction in Europe and the U.S. The Phase III program includes additional clinical studies scheduled to begin in the first half of next year.
Probuphine is designed to provide continuous, long-term therapeutic levels of the drug buprenorphine, an approved agent for the treatment of opioid dependence. The Company believes that Probuphine has the potential to reduce limitations currently associated with daily oral buprenorphine therapy, including poor compliance, variable blood levels, morning withdrawal symptoms before each daily dose, and misdirection of drug.

Drug Pipeline Series: Phase II, Oct23-Oct30, 2006

2006-10-31T13:14:00.000-08:00

OREXIGEN REPORTS RESULTS FROM STUDY OF OBESITY DRUG
Orexigen Therapeutics announced that Excalia, a combination of two centrally acting medications intended to provide and sustain clinically important weight loss, demonstrated significant weight loss in a six-month, double-blind, Phase IIa clinical study. The magnitude of weight reduction exceeded that seen with placebo. The findings showed that patients completing the blinded 24-week phase lost on average 9.2 percent of their weight from baseline using Excalia compared with an average of 0.4 percent weight loss from baseline for patients using placebo. The study results further demonstrate that weight loss continued through an additional 24-week open-label period, with Excalia patients achieving an average weight loss of 12 percent from baseline by 48 weeks.
Excalia is a proprietary combination of bupropion, a dopamine and norepinephrine reuptake inhibitor, plus zonisamide, an approved anticonvulsant medication. The company's preclinical research suggests that combining these two central nervous system drugs acts on a complex of neurons in the hypothalamus, the area of the brain contributing to the regulation of appetite, energy output and maintaining body weight. The compound was tested in a double-blind, placebo-controlled, randomized, proof-of-concept Phase II clinical study of 127 non-smokers with body mass indices (BMI's) between 30 and 40.

RENOVO REPORTS POSITIVE RESULTS FROM SCAR-REDUCTION TRIAL
Renovo has announced positive Phase II clinical trial results for its lead drug, Juvista, in a 12-month proof-of-concept study of scar reduction at split-thickness skin graft donor sites.
Juvista is a therapeutic application of human recombinant TGFß3, which has been shown in clinical trials to markedly improve subsequent scar appearance in the skin. The trial was a fully randomized, double-blind, placebo-controlled study designed to investigate the safety, tolerability, systemic exposure and anti-scarring potential of Juvista in split-thickness skin graft donor sites. Clinical assessment by plastic surgeons at 12 months following administration of Juvista demonstrated a statistically significant reduction in scarring compared with placebo and indicated a permanent regeneration of more normal skin. This trial demonstrates, for the first time, the efficacy of Juvista in the reduction of scarring in large open wounds whose margins are not approximated and sutured.
Juvista was effective given as an injection followed by topical application at the time of surgery and topical application one day later. The study was the first time Juvista has been administered to open wounds and is in contrast to previous trials in incisional wounds closed by suture or steri strips.
Development of a topical formulation of Juvista would offer the prospect of additional indications such as reducing scarring in split thickness skin graft donor sites, grafts and burns which are markets of high medical need. Juvista injection for closed wounds following incisions/excisions, however, remains Renovo's primary target market as this represents the vast majority of surgical procedures.

ViroPharma and Wyeth Initiate Dosing in Phase 2 Study of HCV-796 in Treatment Naive Patients and Non-Responders
ViroPharma Incorporated announced that patient dosing has commenced in a Phase 2 study of HCV-796, a unique orally dosed hepatitis C viral polymerase inhibitor that interferes with the replication of hepatitis C virus (HCV).
The Phase 2 study is being conducted with Wyeth Pharmaceuticals, a division of Wyeth (NYSE: WYE), ViroPharma's partner in development of HCV-796.

The objectives of this trial are to assess the safety, tolerability, pharmacokinetic profile, and antiviral activity of HCV-796, when used in combination with pegylated interferon alfa-2b plus ribavirin compared to the current standard of care in treatment-naive subjects with HCV genotype 1 infection and in patients with HCV genotype 1 infection who were non-responders to prior HCV therapy. The companies will add an additional dose or doses of HCV-796 to the trial to further elucidate the dose response.

MethylGene Initiates Phase I/II Combination Clinical Trial with its Proprietary HDAC Inhibitor, MGCD0103, and Gemzar'R' in Patients with Pancreatic Cancer
MethylGene Inc., along with its partner Pharmion Corporation, announced the initiation of a Phase I/II clinical trial (Trial 006) evaluating its isotype-specific histone deacetylase (HDAC) inhibitor product candidate, MGCD0103, in combination with Gemzar® (gemcitabine HC1; Eli Lilly and Company) in patients with solid tumors, including pancreatic cancer. Gemzar is an approved chemotherapy, marketed for use in pancreatic, non-small cell lung, breast and ovarian cancers.
In the Phase I portion of this open-label trial, MGCD0103 will be given orally, three times per week for four weeks in combination with Gemzar, which will be administered intravenously once per week for three weeks out of four in patients whose cancers are eligible to be treated with Gemzar, or patients who have no available standard of care. Key objectives for this portion of the study will be to evaluate the compatibility and safety of administering these two agents together, to determine the maximum tolerated dose of MGCD0103 and to define the Phase II dose to be administered in this combination. Secondary objectives include determining the dose-limiting toxicities, objective responses, time to progression, survival, and the pharmacodynamic and pharmacokinetic characteristics. In the expanded Phase II portion of the trial, the primary objective is to determine the overall response rate in pancreatic cancer patients. The trial may enroll up to 60 patients at cancer centers in North America. The trial is expected to take 18 to 24 months to complete.

EntreMed Commences Clinical Trial for MKC-1 in Lung Cancer Patients
EntreMed, Inc. announced commencement of a multi-center study with its drug candidate, MKC-1, in non-small cell lung cancer (NSCLC) patients. The lead institution for this Phase 1/2, open label, dose escalation study will be the Indiana University Cancer Center in Indianapolis, Indiana. Nasser H. Hanna, M.D., Assistant Professor, Department of Medicine, Division of Hematology/Oncology at IUCCI, will serve as Principal Investigator. MKC-1 is being evaluated currently in Phase 1 and 2 clinical studies against breast cancer and in patients with leukemia.

The objective of the Phase 1 portion of this study will be to assess the safety and maximum tolerated dose of MKC-1 when administered orally in combination with pemetrexed (Alimta®). Alimta® is a multi-targeted antifolate, which blocks the activity of folic acid and is approved for the treatment of metastatic NSCLC.
The Phase 2 component of this study will assess the antitumor activity and progression free survival (PFS) in up to 60 patients with non-small cell lung cancer. Patients whose disease has progressed following initial therapy may be eligible to enroll. Patients will receive orally administered MKC-1 in combination with pemetrexed (Alimta®). A secondary endpoint of the Phase 2 study will be to evaluate other parameters of antitumor activity including response duration and overall survival.
MKC-1 is a novel, orally active cell cycle inhibitor with in vitro and in vivo efficacy against a wide range of human solid tumor cell lines, including multi-drug resistant cell lines. MKC-1 has demonstrated broad-acting antitumor effects, showing tumor growth inhibition or regression in multiple animal models, including paclitaxel-resistant models. MKC-1 has been shown to inhibit mitotic spindle formation, prevent chromosome segregation in the M- phase (mitosis) of the cell cycle, and induce apoptosis. These effects are consistent with a mechanism resulting from MKC-1 binding to multiple intracellular targets, including tubulin and the importin beta proteins. The importin beta family of proteins plays a critical role in nuclear transport and cell division.

Neurogen Commences Phase II Clinical Trial in Chronic Insomnia Patients
Neurogen Corporation announced that it has commenced a Phase II clinical trial in chronic insomnia patients with the Company's insomnia agent, NG2-73. The study will measure reduction in time to onset of persistent sleep and sleep maintenance across a range of doses and formulations during two weeks of treatment. NG2-73 selectively modulates receptors of the gamma-aminobutyric acid (GABA) neurotransmitter system and is one of several unpartnered compounds in Neurogen's portfolio.
The Phase II clinical trial is a randomized, double-blind, placebo-controlled, multi-center, parallel group study designed to determine the efficacy and safety of five different dose and formulation profiles of NG2-73 compared to placebo. The primary endpoint will be the time it takes to fall asleep as defined by Latency to Persistent Sleep (LPS). Sleep maintenance will be explored in several secondary endpoints. At least 240 chronic insomniacs, aged up to 64 years, are expected to receive study drug or placebo for 14 days. Polysomnography will be used to measure various sleep parameters.

Drug Pipeline Series: Phase I, Oct23-Oct30, 2006

2006-10-31T13:07:00.000-08:00

EPIX Pharmaceuticals Initiates Phase 1 Multiple Ascending Dose Clinical Trial of PRX-07034 in Obesity
EPIX Pharmaceuticals, Inc. announced the initiation of a Phase 1 multiple ascending dose clinical trial to study the safety, tolerability, pharmacokinetics, and pharmacodynamics of PRX-07034 administered once-daily for 28 days in a population of otherwise healthy obese adults with body mass indices between 30 and 42 kg/m(squared). PRX-07034 is a novel, highly selective 5-HT6 receptor antagonist being developed for the treatment of obesity, as well as for cognitive impairment associated with Alzheimer's Disease and schizophrenia.
PRX-07034 is a novel, highly selective, small-molecule antagonist of a specific G-protein coupled receptor (GPCR) known as 5-HT6. Preliminary safety and tolerability data from a recently completed single ascending dose Phase 1 trial in healthy adult male and female volunteers indicated that single doses of PRX-07034 were well-tolerated up to 2500 mg, the highest dose tested. In addition, PRX-07034 demonstrated adequate absorption, with drug exposures increasing with increasing doses and a half-life of 14 to 24 hours, making it suitable for once-daily dosing.

Metabasis Therapeutics Initiates a Phase 1 Clinical Trial of MB07811, a Novel Product Candidate for Reducing Both LDL-Cholesterol and Triglycerides
Metabasis Therapeutics, Inc. announced that it has initiated a Phase 1 clinical trial of MB07811, a novel, orally active product candidate for the management of hyperlipidemia, or elevated cholesterol. MB07811, Metabasis' fifth internally discovered product candidate to enter human clinical trials, uses the Company's proprietary HepDirect® prodrug technology to target a beta-subtype-selective thyroid hormone receptor (TRB) agonist to the liver to reduce serum cholesterol (LDL) and triglycerides (TGs). The Company believes that this drug class has the potential to be additive to the class of hyperlipidemia drugs known as "statins", and preclinical data suggests that MB07811 could be as effective at lowering serum cholesterol as this important drug class. Statins represent a drug class commonly used to treat hyperlipidemia and at present comprise the single largest pharmaceutical market in the world, growing by over 15% per year.
The study initiated will evaluate the safety and tolerability of MB07811 in a rising single dose study in healthy volunteers. Assuming the successful completion of additional preclinical trials and the recently initiated Phase 1 single dose trial, the Company expects to pursue further clinical studies, including a multiple dose Phase 1 study in healthy volunteers.

INNOVIVE Pharmaceuticals Begins Enrollment in Phase I Study of INNO-305 Peptide Immunotherapy in AML, MDS, Mesothelioma and Non-Small Cell Lung Cancer
INNOVIVE Pharmaceuticals, Inc. announced that a Phase I clinical trial investigating INNO-305 in acute myelogenous leukemia (AML), myelodysplastic syndrome (MDS), mesothelioma and non-small cell lung cancer (NSCLC) has enrolled its first patient. The trial is being conducted by Lee Krug, M.D., of the Thoracic Oncology Service, and Peter Maslak, M.D., of the Leukemia Service at Memorial Sloan Kettering Cancer Center in New York.
The study is an open label fixed dose trial and will study the safety, tolerability, pharmacokinetics and preliminary efficacy of INNO-305. The vaccine will be tested in patients with hematologic malignancies and solid tumors for which there is evidence of WT1 expression.
INNO-305, a WT1 peptide therapeutic vaccine, is unique among WT1 peptide immunotherapies because of its ability to stimulate both CD8 and CD4 T-cells. It is believed that stimulating both types of T-cells may result in a more robust and ubiquitous immune response. As an added measure, INNO-305 utilizes an approach in which the wild-type WT1 peptide sequences are altered to improve the ability of the drug to activate T-cells.

Anesiva Starts Phase 1 Clinical Study of 1207, New Topical Local Anesthetic
Anesiva, Inc. announced that it has commenced Phase 1 clinical testing of product candidate 1207, a new topical local anesthetic for the potential treatment of numerous pain conditions, including neuropathic pain.
The study, designed to assess the safety of 1207, will enroll 24 adult healthy male volunteers in up to six dose-escalating cohorts in Australia. In addition to safety data, the randomized, double-blind, placebo-controlled study will measure sensory perceptions of touch and warmth following a single topical administration of 1207 compared with placebo.
1207 is a new chemical entity with novel anesthetic properties that provide pain relief by binding to the fast sodium channel on neurons responsible for transmitting pain signals from nerve endings to the brain. Specifically, 1207 binds to the fast sodium channel on both A nerve fibers responsible for transmitting immediate "adaptive pain" signals and C nerve fibers responsible for transmitting longer-term, dull, aching throbbing pain signals. By interrupting the communication channel of both A fibers and C fibers, 1207 is designed to provide effective topical pain relief with a faster onset and longer duration of action than currently marketed pain products. In preclinical testing, topical administration of 1207 demonstrated a long duration of action and deep, rapid penetration. Other potential applications for 1207 include pre-procedural use in dermatological surgery and post-surgical incision pain.

Tanox Initiates Phase 1 Clinical Trial Evaluating TNX-650 for Treatment of Asthma
Tanox, Inc. has begun dosing a Phase 1 clinical trial of TNX-650, a humanized monoclonal antibody being evaluated as a potential treatment for moderate-to-severe asthma.
The trial is a randomized, double-blind, placebo-controlled, dose- escalation study of the safety, tolerability and pharmacokinetics of single doses of TNX-650 in healthy volunteers. A total of 32 subjects will be enrolled in four cohorts in the study, which is being conducted at a single site in the U.S.
TNX-650 targets Interleukin 13 (IL-13). Preclinical studies indicate that IL-13 is a key mediator of asthma responses, including airway inflammation, obstruction and hyper-reactivity. TNX-650, which has a mechanism of action unique from currently available asthma treatments, has the potential to be a therapeutic option for patients whose disease is not currently well controlled and for non-allergic asthmatics.

Researchers Seek Key To Antiaging

2006-10-30T11:57:00.000-08:00

In the 1930s, researchers stumbled onto a surprisingly simple way to slow the biological forces of aging: cutting normal calorie intake by about a third. Scientists found it boosts animals' life spans by 30% to 40%, and considerable evidence suggests that calorie restriction, or CR, would slow human aging too.

But only steely ascetics could hack its hunger pangs. So the finding remained a little-known curiosity in the back halls of science.

Now a coterie of scientists and biotech ventures are rekindling interest in CR as they try to mimic its antiaging effects with medicines. It is still a highly speculative quest, and many researchers fret that it hasn't completely shaken its association with centuries of dubious nostrums to slow aging, from inhaling virgins' breath to eating gold to implanting monkey glands.

Much of the new focus is on a substance in red wine called resveratrol. The interest in it started three years ago when a group led by Harvard Medical School biologist David Sinclair reported that it boosted yeast cells' life span by 70% via a mechanism resembling CR. He later co-authored a study showing that it also boosts life span in fruit flies and roundworms. But his tendency to make bold leaps based on tentative data has also sparked intense controversy. One big question: Does he really understand the workings of CR well enough to mimic them in a drug?

Last spring, Italian scientists reported that resveratrol boosted life span more than 50% in a kind of short-lived fish. Intriguingly, fish on resveratrol had much faster swimming speeds as they aged, and spent far more time moving around, than did undosed control fish.

At least two groups of researchers are now testing whether resveratrol can extend life span in mice -- the first such studies in mammals. At a meeting of the American Aging Association in June, Dr. Sinclair and colleagues presented preliminary results from a study showing that resveratrol had "CR-like protective effects" against the buildup of fatty deposits in the livers of mice on high-calorie diets. That suggests that resveratrol could lead to new drugs for diseases of aging associated with rich diets, such as adult-onset diabetes.

A company that Dr. Sinclair co-founded in 2004, Sirtris Pharmaceuticals Inc., of Cambridge, Mass., has begun testing a resveratrol-based drug in diabetic patients. It has raised $82 million from venture capitalists, a hefty sum for an early-stage biotech. (Sirtris's chief executive, Christoph Westphal, is married to a reporter for this newspaper.)

It faces competition from Elixir Pharmaceuticals Inc., also based in Cambridge, which Dr. Sinclair's former mentor, Massachusetts Institute of Technology biologist Leonard Guarente, co-founded in 1999 to develop drugs based on gene variants that slow aging. The niche also includes BioMarker Pharmaceuticals of Campbell, Calif., and LifeGen Technologies of Madison, Wis., both of which focus on mimicking CR with drugs.

The companies hope to develop therapies for diseases, not antiaging pills. One reason is that the Food and Drug Administration doesn't recognize aging as a problem warranting treatment. But if a drug could retard aging, it might delay the onset and possibly the progression of age-related diseases. "When you slow aging," says University of Illinois epidemiologist S. Jay Olshansky, "you push a host of diseases to later ages at one fell swoop -- cancer, heart disease, Alzheimer's, diabetes, as well as everything else that's negative about growing older."

Some researchers believe antiaging drugs could also improve health in late life -- rather than prolong misery -- letting people stay in relatively good shape until a swift demise. Their case rests partly on the svelte, energetic look of old animals on CR. "Often it's hard to identify the cause of death" in post-mortem studies on such animals, says Richard Weindruch, a University of Wisconsin CR researcher. "The only apparent problem is that they died."

Still, some experts on aging doubt that enough is known about CR to guide the development of drugs that mimic its effects. "We know a lot about CR's effects," says Edward Masoro, a leading gerontologist. "But what bothers me is that I don't think we've figured out CR's basic mechanism yet."

Dr. Sinclair's idea that resveratrol mimics CR has come under heavy fire. His main adversaries are two researchers who used to rub elbows with him when they all studied together with MIT's Dr. Guarente. The skeptics maintain that resveratrol's mode of action is still murky; instead, they are looking at other mechanisms that may account for how CR works.

The resveratrol doses used in the life-span-extension studies in animals were far higher than the amount people can get by drinking wine -- they were roughly equivalent to hundreds of glasses a day. Resveratrol is available as a dietary supplement, but to replicate the doses used in the studies, a person would need to take scores of pills a day. (Sirtris says it is developing prescription drugs that work like resveratrol but are hundreds of times more potent.) The dietary supplements haven't been tested in clinical trials, so their efficacy isn't proven, nor is it clear what dose might make people live healthier or longer. And although they seem safe at modest doses, megadoses may not be.

Nevertheless Dr. Sinclair, a 37-year-old Australia native, thinks taking small doses over time may yield health benefits and has been taking the supplements for three years.

The story of resveratrol has its roots in scientists' increased understanding of CR. In 1989 researchers theorized that it activates a "starvation response" whose genetic machinery evolved eons ago to enable survival through periods of food shortage -- such as droughts -- by retarding the rate of aging. The response blocks growth and reproduction in order to free up energy to slow aging. The energy is siphoned to cellular systems that limit damage from harmful "free radical" molecules and other toxins produced as metabolic byproducts in cells.

The theory explained longstanding mysteries about CR, such as the fact that animals on CR become resistant to toxic chemicals and temporarily lose the ability to reproduce. It also had a dismaying implication: Our obesity-fostering, high-calorie diets are putting us in fast-aging-and-reproducing mode. That may be why childhood obesity is closely linked to early puberty, which now begins before age eight in many girls, and why adult obesity is linked to such a wide swath of aging diseases -- cancer, heart disease, diabetes, arthritis, even Alzheimer's.

But an important piece of CR's machinery remained hidden: the activator that senses calorie intake and, when it is low, triggers cellular changes that retard aging. This CR off-on switch is the holy grail of gerontology, the study of aging. In principle, drugs that turn it on could ward off or ameliorate degenerative diseases of aging, just as CR does in animals.

Many scientists are looking for the switch. And to the consternation of some of them, Dr. Guarente, 54, and Dr. Sinclair assert that they know what it is. Further, Dr. Sinclair's research indicates that resveratrol toggles it in order to slow aging. Their shared view on CR's basic mechanism has sparked a furious debate.

Its roots go back to 1991, when Dr. Guarente's lab at MIT began hunting for life-span-boosting mutations in baker's yeast.

The grandson of Italian immigrants, Dr. Guarente grew up in Revere, Mass., a blue-collar town near Boston. In his memoir "Ageless Quest," he recalls that as a child, "I was precocious by local standards -- I quit smoking in third grade."

By the mid-1990s, Dr. Guarente's lab had zeroed in on so-called SIR, or silent information regulator, genes. SIR mutations enabled yeast cells to divide an abnormally large number of times before dying, a form of extended life span. But how they worked wasn't clear until the group made further discoveries, one of which was Dr. Sinclair's first claim to fame.

Dr. Guarente recalls that Dr. Sinclair, who came to MIT in 1995 to do post-doctoral studies, breezed into his lab as if out of a Crocodile Dundee movie, greeting everyone with a cheery, "Hello, mate." The eldest son of parents who both worked in medical diagnostics, he was known in high school as a talented class clown and risk-taker, a kid who aced science classes but got in trouble for setting off minor explosions in chemistry lab. The idea of taking part in unorthodox, high-risk studies on aging suited him.

In a key experiment, Dr. Sinclair showed that yeast cells' machinery for copying chromosomes runs amok as the cells age, eventually killing them. Hailed as a major advance, the discovery got Dr. Guarente on Good Morning America. It also helped him formulate a theory positing that proteins made by SIR genes activate CR's antiaging action. A SIR gene found in mammals, dubbed SIRT1, seems especially important: It makes a protein that Drs. Guarente and Sinclair believe triggers the slowed-aging mode in mammals when calorie intake is low. In their view, it's either the gerontological grail or a crucial part of it -- hence, stimulating it might slow aging.

Drugs that juice up proteins' activity are very rare. But in 2003, Dr. Sinclair, then at Harvard, heard that scientists at Biomol International LP, a Plymouth Meeting, Pa., biotech firm, had observed signs of SIRT1 activation in test-tube experiments with certain plant compounds. The most promising one was resveratrol. That was doubly exciting, for dozens of studies on the red-wine ingredient had previously suggested that it lowered the risks of heart disease, cancer and various other disorders of aging -- just what a substance that slows aging should do.

Dr. Sinclair soon began the study about resveratrol's effects on yeast aging. But a year after it appeared, studies by other researchers cast doubt on the idea that SIR genes are key actuators of CR.

The sharpest questions were raised by two researchers who also studied under Dr. Guarente: University of Washington biologists Brian Kennedy and Matt Kaeberlein. Their data suggest that CR can exert antiaging effects independently of SIR genes, and that other genes are more central to CR -- at least in yeast. "My view is that CR probably has nothing to do" with SIR genes in lower animals, says Dr. Kaeberlein. In short, according to him, Drs. Guarente and Sinclair haven't necessarily found the grail.

Undaunted, Dr. Sinclair joined forces with a researcher at the National Institute on Aging, Rafael de Cabo, to plan one of the ongoing studies of resveratrol in mice. But he had a problem: He lacked the $20,000 needed to buy mice. Then he got a call out of the blue from Tom LoGiudice, foreman at the U4EA ("euphoria") Ranch near Thousand Oaks, Calif. Mr. LoGiudice had phoned on behalf of the ranch's owner, Harman Rasnow, who was considering taking resveratrol pills and wanted to know more about them. When Mr. LoGiudice heard about Dr. Sinclair's problem, he arranged for his boss to talk directly to the researcher. "I have an 85-year-old passion for longevity," says Mr. Rasnow, pinpointing his age. "David sounded like he was really onto something. So I told him, 'I'll send you a check for $20,000.'"

Dr. Sinclair later got another call from Mr. LoGiudice, this time inviting him to make a pitch for funding to one of Mr. Rasnow's wealthy acquaintances, Paul Glenn, a venture capitalist and a longtime supporter of research on aging. After Dr. Sinclair did so, the Glenn Foundation for Medical Research in Santa Barbara, Calif., awarded $5 million to Harvard Medical School to launch a center on the basic mechanisms of aging with Dr. Sinclair as its founding director. Now plans are afoot to expand the center into a leading institute on aging, says Mr. Glenn, with start-up funding of $75 million to $100 million.

Sirtris, the company Dr. Sinclair co-founded, says it has made progress. Test-tube and animal studies suggest that its early-stage drugs may help treat various neurological killers as well as diabetes, says Dr. Westphal. The company plans soon to begin testing a drug in people with MELAS syndrome, a rare metabolic disorder that afflicts youngsters with potentially fatal brain and muscle deterioration.

At a recent meeting on aging research, a Sirtris scientist reported that SIRT1-activating compounds, including resveratrol, dramatically lowered blood levels of glucose and insulin in mice that get diabetes on high-fat diets, as well as helped to keep their weight down -- just as CR does.

---

Key antiaging medical advances: 1935: Cornell scientists report calorie restriction's antiaging effect in rodents. 1956: University of Nebraska researcher proposes that "free radicals" cause aging, indicating that antioxidants may slow it. 1989: U.S. and British scientists propose that calorie restriction triggers an evolutionarily ancient "starvation response" to slow aging. 1992: University of California at San Francisco researchers find a gene mutation that doubles life span in roundworms. 1996: Southern Illinois University scientists report gene mutation that extends life span in mice. 2000: MIT's Leonard Guarente and colleagues report that "SIR" genes actuate calorie restriction's antiaging effects in yeast. 2003: Harvard's David Sinclair and others report that resveratrol, a substance in red wine, extends yeast life span. February 2006: Italian scientists report resveratrol extends life span of a fish species.

6-Month Xience Diabetic Data Little-Changed

2006-10-30T11:56:00.000-08:00

Abbott Laboratories Inc. (ABT) released more data for its Xience V drug-coated stent late Wednesday, showing very similar performance at six months in avoiding blood-vessel diameter changes with complex diabetic patients as with the other cases.

Other data in the Spirit II trial, meanwhile, showed no additional major heart problems in the six-to-nine-month timeframe.

Stents are tiny mesh tubes that prop open arteries, and drug-coated stents like Xience use medication to slow cell growth that can re-narrow arteries and lead to complications. Diabetic patients present more challenging stent cases, and also make up a sizable portion of stent recipients.

A subset of diabetic patients in the 300-patient Spirit II trial showed "nearly identical rates of in-stent late loss," or a measure of how vessel diameter changes at six months, Abbott said in a release. Abbott presented the latest Xience details at the Transcatheter Cardiovascular Therapeutics conference in Washington, D.C.

The Abbott Park, Ill., company garnered attention last month with the release of six-month data that showed Xience had better late-loss performance than Taxus, a popular stent made by industry giant Boston Scientific Corp. (BSX).

For diabetic patients in the trial, in-stent late loss was 0.15 millimeters for Xience versus 0.39 millimeters for Taxus at six months, Abbott said. This is comparable with the study's overall six-month results.

"We believe these results have the potential to differentiate Xience V for physicians with patients whose cases present more challenges for treatment," said John Capek, president of cardiac therapies in Abbott's vascular business, in the release.

The issue of stent safety has been a dominating topic at the cardiology conference. Specifically, talk and presentations have focused on the issue of late-stent thrombosis, or clots that form around a stent months or years after implantation.

Abbott said there were no additional cases of major adverse cardiac events or stent thrombosis in the Spirit II trial between six and nine months. In that time span, the major heart event rate stood at 2.8%, while the stent thrombosis rate stood at 0.5%, Abbott said.

Abbott significantly bolstered its stake in the stent sector through its April acquisition of Guidant Corp.'s vascular and endovascular business, a deal that included Xience. Abbott recently announced plans to drop its home-grown ZoMaxx drug-coated stent program amid poor data, but also just introduced the Xience in Europe slightly ahead of schedule.

Speaking during a conference with analysts on Monday, Capek said "the customer feedback has been remarkable" with Xience after just a few weeks on the market. He also said Abbott remains on track to introduce the stent in the U.S. in the first half of 2008 and in Japan in 2009, pending regulatory approval.

Xience data has bearing for Boston Scientific beyond the Taxus comparison, as Boston Scientific bought the bulk of Guidant through April's deal and agreed with Abbott to share rights to the Guidant stent program. Boston Scientific announced last week that it had received regulatory approval to market Promus, its version of Xience, in the European Union.

AstraZeneca Halts Development Of Key Drug

2006-10-30T11:55:00.000-08:00

In a severe setback for a company that has stopped development of several drugs over the past two years, AstraZeneca Plc (AZN) said Thursday it's terminating development of its experimental stroke drug NXY-059 after it didn't reveal any benefit in a trial.

The drug failure leaves AstraZeneca, which is one of the world's biggest pharmaceutical companies, with only one potential blockbuster drug in late-stage development.

Lacking a significant number of drugs that will be able to compensate for declining sales once its bestsellers lose patent protection, AstraZeneca will now probably look even more aggressively for opportunities to buy the marketing rights to drugs developed by smaller companies, analysts said.

Speaking to reporters during a conference call, AstraZeneca Executive Director of Development John Patterson said the latest setback won't change the company's strategy of bolstering its pipeline through in licensing and acquisitions.

"We have made quite clear that we saw this as a high-risk project," Patterson told reporters.

Navid Malik, an analyst with London-based brokerage Collins Stewart, said that while AstraZeneca can maintain short-term growth by continuing its cost cutting strategy, "it desperately needs to bring new products to the market, without which no amount of cost cutting will help future earnings growth."

AstraZeneca shares slumped on the news. At 0832 GMT, they were down 4.5%, or 159 pence, at 3370p in a broadly higher London market.

Patterson said the study had proved that drugs like NXY-059, which aim to protect the patient's brain from further damage after a stroke, don't work.

"This is a sad day for patients with ischemic stroke, and a sad day for us," he said.

Analysts at Deutsche Bank AG had forecast peak sales of around $750 million for the drug, which was in an intermediate phase of development.

"The setback is likely to prompt investors to question the breadth and risk profile of the late-stage pipeline, as well as any impact the setback will have on AstraZeneca's in-licensing and mergers & acquisitions strategy," Deutsche Bank analysts said in a note to investors.

NXY-059 was licensed under a 15% royalty pact from Renovis Inc. (RNVS). AstraZeneca will now hand back the rights to the drug to Renovis, Patterson said.

Shares in Renovis, a biotech company headquartered in San Francisco, California, closed at $14.21 in New York Wednesday.

AstraZeneca is now left with a very thin pipeline after the recent expensive failures in late-stage testing of drugs such as blood-thinner Exanta, lung cancer drug Iressa and Galida for diabetes.

AstraZeneca's costs associated with discontinuing NXY-059 will be small at around $12.5 million, Patterson said.

Dropping the drug from the pipeline leaves AstraZeneca with just one other potential blockbuster in development: cardiovascular drug AGI-1067, which is in phase III testing, the latest step in development before a drug can be filed for regulatory approval.

Sanford Bernstein analyst Gbola Amusa said AstraZeneca's remaining key drug candidate will be now particularly important for sentiment.

The once-daily treatment for atherosclerosis, a build up of plaque and fat inside arteries, is expected to report results from current phase III trials in the first half of 2007.

AstraZeneca is due to post its third quarter earnings at 1000GMT Thursday.

Analysts expect the company to deliver a strong set of results, driven by key drugs Nexium, a heartburn treatment, and cholesterol-lowering treatment Crestor, which have seen strong prescription growth during the quarter, but also tight cost management.

AstraZeneca third-quarter operating profit is expected to advance 22% to $2.07 billion on sales rising 12% to $6.51 billion.

Company Web Site: http://www.astrazeneca.com

Panel OKs Shingles Vaccine For Elderly

2006-10-30T11:53:00.000-08:00

For the first time in almost 30 years, a government panel is adding a vaccine, for shingles, to the list of preventive shots recommended for older adults against debilitating or life-threatening illnesses.

The Advisory Committee on Immunization Practices voted yesterday to recommend Merck & Co.'s new Zostavax vaccine for shingles in people over age 60. The committee of doctors and immunization experts convenes three times a year to shape vaccination policy for the Centers for Disease Control and Prevention, and its recommendations help determine both medical practice and insurance coverage policies.

Until now, the major vaccines recommended for older Americans have been to protect against flu and pneumonia.

The Food and Drug Administration approved Zostavax in May to prevent shingles, or herpes zoster, in patients over 60. Shingles emerges in people who have had chickenpox after the dormant virus reactivates in older adults. The virus causes pain and ultimately erupts on the skin as blisters and rash. About one million cases of shingles are reported annually in the U.S., of which 250,000 turn into more severe postherpetic neuralgia, or chronic nerve pain, according to Mark Feinberg, vice president for medical affairs and health policy in Merck's vaccine division.

The market -- and the CDC nod -- represents a boon for Merck, the only company selling a shingles vaccine, but the product won't necessarily be a blockbuster, analysts said. Zostavax had $11 million in third-quarter sales. With an estimated 50 million Americans over age 60 -- a population that stands to increase as baby boomers reach that age -- analysts estimate annual sales may approach $1 billion but more likely will top off around $600 million.

Unlike vaccines for school children, the shingles vaccine isn't required. "With seniors, there are questions about whether to go to the doctor, whether they want the vaccine," said Barbara Ryan, a pharmaceutical analyst at Deutsche Bank, who said she thinks the vaccine could potentially reach $400 million in U.S. sales. "There are a lot of reasons not everyone chooses to get vaccinated."

The one-dose, roughly $150 vaccine is a more potent version of Merck's chickenpox vaccine approved in 1995. In a large clinical trial, Zostavax reduced the incidence of shingles by 51% and the risk of long-term pain by two-thirds. The condition occurs most frequently in older people, yet Merck is testing Zostavax in younger age groups in hopes of expanding the market, Dr. Feinberg says.

"Shingles can be a pretty debilitating illness, and postherpetic neuralgia causes excruciating pain that has been very challenging to treat," said Sharon Brangman, a specialist in geriatric medicine at SUNY Upstate Medical University, in Syracuse, N.Y.

Dr. Brangman, a board member of the American Geriatrics Society, looks to the government recommendations to determine how to treat her roughly 3,000 elderly patients. Until now, though, she hasn't administered Zostavax, to be cautious with new medicines and mindful of how they may interact with the many treatments older patients tend to require.

"You don't want to give them something that makes it worse," she said.

Some health-care plans, such as Aetna Inc., began covering the vaccine when it came out. Others, such as Cigna Corp. and WellPoint Inc., are updating their plans based on the panel's recommendation. Merck estimated that plans covering 43% of insured patients reimbursed for the vaccine before the panel's recommendation. The vaccine costs $3 for so-called dual-eligible Medicare and Medicaid patients, while people in health plans may pay up to a 25% co-pay on the list price of about $150, Merck said.

FDA OKs Novartis' Drug For Chronic Hepatitis B

2006-10-30T11:50:00.000-08:00

The U.S. Food and Drug Administration said Wednesday that it approved Novartis AG's (NVS) drug Tyzeka for the treatment of chronic hepatitis B.

The drug, a once-daily tablet, was developed by Idenix Pharmaceuticals Inc. (IDIX) with Novartis under a development and commercialization pact.

American depositary shares of Novartis, which is based in Switzerland, closed Wednesday at $60.74, up 42 cents, while shares of Cambridge, Mass.-based Idenix closed at $9.85, up 9 cents. In after-hours trading, Idenix rose 2% to $10.05 while Novartis was unchanged.

According to the FDA, a yearlong trial showed antiviral effectiveness of the drug, including the suppression of hepatitis B virus, and improvement in liver inflammation comparable to Epivir-HBV, one of five other medications approved to treat patients with the condition.

Novartis said in an email that in the phase III of the trial, 56% of all Tyzeka-treated patients achieved undetectable levels of the virus in the first 24 weeks of treatment. The virus remained undetectable at one year in 95% of those patients.

Chronic hepatitis B attacks the liver and can cause lifelong infection, scarring of the liver, and eventually liver cancer, liver failure and death.

The virus is spread when blood from an infected person enters the body of someone who isn't infected, sometimes by sexual contact or blood contamination.

An estimated 1.25 million Americans are currently infected with the virus, and 350 million people are infected worldwide. The disease is responsible for up to 1.2 million deaths each year, according to Novartis.

Side effects of the drug included upper respiratory tract infection, fatigue, headache, abdominal pain and cough, the FDA said.

In addition, after several weeks to months of Tyzeka use, some patients developed symptoms ranging from transient muscle pain to muscle weakness.

The agency also said that using Tyzeka hasn't been shown to reduce the risk of infecting others with hepatitis B.

Seeking Pain Pill Minus Gut, Heart Woes

2006-10-30T11:48:00.000-08:00

Two drug companies hope to make a better arthritis drug with one pill that's a combination of a 30-year-old painkiller and a popular heartburn treatment. In the process they will seek to fill a void left when Vioxx was pulled from the market two years ago over safety concerns.

AstraZeneca PLC (AZN) of the U.K. and Pozen Inc. (POZN), Chapel Hill, N.C., recently formed a collaboration to develop a fixed-dose combination of naproxen, which is a generic pain reliever sold under the prescription brand Naprosyn and over-the-counter as Aleve, plus Nexium, AstraZeneca's blockbuster heartburn pill that racked up $4.6 billion in sales last year.

The companies plan to market the product as a treatment for pain associated with osteoarthritis and rheumatoid arthritis in people at risk for developing gastric ulcers caused by certain painkillers. Initially it would be a twice-a-day treatment, according to Pozen Chief Executive John Plachetka.

There are risks, however. As yet, there are no clinical data to prove the single-pill combination will work. And naproxen's label currently carries a warning that it can increase the risk of heart attack or stroke. A patient trial is expected to begin next year, and the drug is probably at least a couple of years away from reaching the market.

But the plan is to offer naproxen's pain relief while Nexium, known as a proton-pump inhibitor, alleviates some of naproxen's gastrointestinal side effects such as ulcers and bleeding.

"The idea is to produce a dosage form where the protectiveness of the product is released and deployed before" the gastrointestinal harm of naproxen occurs, Plachetka said in an interview.

Some arthritis specialists already prescribe naproxen and proton-pump inhibitors, or PPI's, to be taken together as separate pills. One company, Tap Pharmaceutical Products Inc., markets naproxen and the PPI Prevacid as separate pills in one package called Prevacid NapraPac. But Pozen and AstraZeneca believe a combination pill would be more convenient for patients and more effective in guarding against gastrointestinal problems.

If it works, Pozen and AstraZeneca think the single-pill combination could invade territory once dominated by a class of painkillers known as Cox-2 inhibitors. These drugs, including Merck & Co.'s (MRK) Vioxx and Pfizer Inc.'s (PFE) Celebrex, were designed to reduce the gastrointestinal side effects seen in older drugs like naproxen.

Merck's withdrawal of Vioxx from the market over safety concerns in 2004, however, raised questions about the cardiovascular risks of Cox-2 drugs. Merck said a study showed Vioxx elevated the risk of heart attack and stroke in people taking it for at least 18 months. In an earlier study involving both Vioxx and naproxen, there were five times as many heart attacks among those taking Vioxx as in the naproxen group.

A combination naproxen-Nexium could go after Celebrex, which remains on the market but with a warning on its label that it may cause an increased risk of heart attack and stroke. One government study found a two- to three-fold risk of heart attack, stroke or other cardiovascular events associated with Celebrex, compared with a fake pill, or placebo.

Another Cox-2, Pfizer's Bextra, also was withdrawn from the market last year over safety concerns. In 2004, the three main Cox-2 inhibitors - Vioxx, Celebrex and Bextra - had combined sales of more than $6 billion. But last year sales of Celebrex, the only Cox-2 left on the U.S. market, had fallen to $1.7 billion from $3.3 billion the year before.

Naproxen isn't free of concerns about cardiovascular safety, however, and while one study suggested it was safer on the heart than Vioxx, it's unclear whether naproxen is safer on the heart than Celebrex.

In late 2004, the National Institutes of Health said a study showed an apparent increase in risk for heart attacks, strokes or other cardiovascular events among people taking naproxen when compared to those on placebo. There was no significant increase in risk for Celebrex in the same NIH trial, which was designed to study whether the drugs could prevent Alzheimer's disease. NIH suspended use of both drugs in the trial, noting a separate study had raised questions about Celebrex's cardiovascular risk.

Still, some industry watchers believe naproxen is among the safest on the heart of all nonsteroidal anti-inflammatory drugs, or NSAID's, which include Cox-2's as well as older painkillers such as ibuprofen, sold under the brands Advil and Motrin, and diclofenac, sold as Voltaren.

"It's a smart idea," Steven Nissen, chairman of cardiovascular medicine at the Cleveland Clinic, said of the proposed naproxen-Nexium combination. "Naproxen, in all the studies, looks like it is very neutral from the point of view of cardiovascular risk.... However, it can be very hard on the stomach, and there is some data suggesting if you give a PPI that reduces stomach acid, it can reduce the risk of GI ulcer and bleeding."

Nissen is lead investigator of a large trial to study the relative heart safety of Celebrex, naproxen and ibuprofen. In the Pfizer-funded study, patients also are receiving a PPI to protect their gastrointestinal tracts, Nissen said, and the study will monitor gastrointestinal events.

David Graham, a drug-safety researcher for the Food and Drug Administration, recommended in the medical journal JAMA last month that generic naproxen plus a PPI would be less costly, equally as effective, and "probably safer" than low-dose Celebrex. He was referring to taking the drugs as separate pills.

Graham's JAMA editorial accompanied an analysis by other researchers suggesting naproxen didn't alter the risk of cardiovascular events; and that a lower dose of Celebrex didn't increase cardiovascular risk, but a higher dose appears to increase risk.

Gail Cawkwell, Pfizer's senior medical director for Celebrex, noted that all NSAIDs carry the same boxed warning about cardiovascular risk, and there was "no way to confirm that one medication is safer than the other for the heart" based on present data.

Some industry watchers question whether a combination pill is necessary given the availability of generic naproxen and over-the-counter PPI's. In an interview, Graham of the FDA said he fears that marketers would try to charge a higher price for a naproxen-Nexium combination pill than that of generic naproxen plus a PPI.

"You can take two tablets for a very low cost," said Graham, who emphasized he wasn't speaking for the FDA. "Unless the proposal to combine the medications together would be at the price of a generic, it's hard to sort of rationalize the increased expense."

AstraZeneca and Pozen say it's too early to talk about pricing for their combination product. According to drugstore.com, a month's supply of Nexium sells for between $136 and $148, depending on the dosage. A month's worth of Celebrex was listed at between $60 and $145, depending on dosage. A month's supply of Prevacid Naprapac costs about $137, according to drugstore.com.

Pozen's Plachetka suggested the combination pill's convenience would be a good selling point.

"People will end up skipping that PPI if they have to take it as a separate pill," Plachetka said. "In our combination product, they can't skip it. I don't think you can put a price on that."

Also, Plachetka thinks a combination naproxen-Nexium would be more effective than a separate-dose regimen in protecting against gastrointestinal side effects. He said Pozen has a proprietary drug-delivery system designed to immediately release the PPI upon ingestion, while delaying release of the naproxen if necessary to protect the stomach.

Pozen and AstraZeneca aren't the only companies trying to develop a new naproxen-based painkiller. NicOx SA (7413.FR) of France is developing naproxcinod, a combination of naproxen and the company's proprietary technology based on nitric oxide. NicOx says the drug has the potential for good gastrointestinal tolerability and safety, with no harmful effects on blood pressure. Data from a late-stage study of the drug are expected to be released soon.

KEY COUNTRY DRUG PURCHASES - RETAIL PHARMACIES

2006-10-27T11:40:00.000-07:00

KEY COUNTRY DRUG PURCHASES - RETAIL PHARMACIES
RETAIL DRUG MONITOR: 12 MONTHS TO June 2006
For all the ATC Main Groups
CARDIOVASCULAR, CENTRAL, ALIMENTARY/, RESPIRATORY, ANTI-INFECTIVES, MUSCULO-SKELETAL
GENITO-URINARY, CYTOSTATICS, BLOOD AGENTS, DERMATOLOGICALS, SENSORY ORGANS
DIAGNOSTIC, SYSTEMIC HORMONES, MISCELLANEOUS, HOSPITAL, PARASITOLOGY