Novartis Files Drugs For Approval Ahead Of Plan

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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.