Pipeline Summaries from Sep 25, 06 till Oct 2, 06

Bulresearch Inc has summarised for you all events for the week Sep 25 - Oct 02, the information about all the drugs in development is available at www.chartsbank.com/PipelineList.aspx , subscription start at 20 USD


EntreMed Commences MKC-1 Clinical Trial in Leukemia Patients EntreMed, Inc. announced commencement of a Phase 1 study with its clinical-stage drug candidate, MKC-1, in patients with hematological (blood) malignancies.
The study will be conducted at the University of Texas MD Anderson Cancer Center in Houston, Texas. Francis J. Giles, M.D., Professor, Department of Leukemia at the MD Anderson Cancer Center, will serve as Principal Investigator. MKC-1 is also being evaluated currently in a Phase 2 clinical study in patients with metastatic breast cancer.
Patients with relapsed or refractory leukemias will be enrolled. At the present time, there is a need for more effective therapies for patients with relapsed or refractory leukemias. MKC-1 has shown good activity against a variety of hematological cell lines leading to interest in a clinical trial in patients with leukemias.
MKC-1 is a novel, orally active cell cycle inhibitor with in vitro and in vivo efficacy against a wide range of human solid tumor cell lines, including multi-drug resistant cell lines. MKC-1 has demonstrated broad-acting antitumor effects, showing tumor growth inhibition or regression in multiple animal models, including paclitaxel-resistant models. In addition to the strong preclinical activity of MKC-1 towards solid tumor lines, the lack of neuropathy and cardiotoxicity seen in clinical trials suggests that MKC-1 may also be valuable in the treatment of hematological cancers.



First Clinical Trial Launched by MDS Nordion to Study Innovative Cancer TreatmentMDS Nordion has received approval from the U.S. Food and Drug Administration (FDA) to begin the first clinical trial for a non-invasive, innovative cancer therapy.
This treatment called TheraSphere® has been developed for patients with liver cancer. The clinical trial, expected to begin in October, will enrol up to 150 patients with secondary liver cancer from five existing TheraSphere® treatment centers in the United States.
TheraSphere® offers another option to the limited number of treatments available for patients suffering from secondary liver cancer. With this treatment, tiny radioactive glass beads attack cancerous tumours in the liver, while minimizing the impact on the patient's healthy tissues. Unlike chemotherapy, it has few side effects. Patients rarely experience extreme fatigue, nausea and vomiting usually associated with high-dose, systemic chemotherapies. The treatment can generally be administered on an outpatient basis as it does not usually require an overnight hospital stay.
TheraSphere®, Yttrium-90 glass microspheres, is a low toxicity, out-patient liver cancer therapy which consists of millions of small glass beads (20-30 micrometers in diameter). Each bead has radioactive Yttrium-90 in it. The physician injects TheraSphere® into the main artery of the patient's liver through a small tube (catheter) and the tiny radioactive glass beads are delivered directly into the liver tumour via blood vessels. The radiation delivered destroys the tumour cells from within the tumour, with minimal injury to surrounding health liver tissue. The Yttrium-90 in TheraSphere® becomes Zirconium-90 as it loses radioactivity. The radioactivity half-life of Yttrium-90 is 64.1 hours resulting in most of the radioactivity disappearing in approximately 10-12 days following treatment with TheraSphere®.



OREXIGEN™ Therapeutics Reports Positive 24-Week Results for Contrave™ Phase III Obesity Treatment Study
OREXIGEN™ Therapeutics, Inc. announced that top line results for the company's lead obesity compound, Contrave™, demonstrated significant advantages in weight loss in a 24-week multi-center, placebo-controlled phase III trial; the trial will continue unblinded for an additional 24 weeks.
Contrave is a proprietary combination of bupropion, a dopamine and norepinephrine reuptake inhibitor, with one of several different doses of naltrexone, an opioid antagonist used to treat various addictive disorders. The bupropion/naltrexone combination is based on the company's underlying research into the brain's regulation of appetite and energy expenditure, which suggests that combining these two central nervous system drugs may improve the ability to initiate weight loss, and importantly, to continue weight loss by blocking the body's attempts to compensate for weight loss during the treatment. The trial is testing three different dosages of naltrexone combined with the same dosage of bupropion. In what may become the preferred dose pairing based on performance and tolerability, patients completing the 24-week trial using Contrave experienced on average an excess of 7% weight loss from baseline compared to approximately 1% weight loss from baseline on average for patients using the placebo.



Anacor Phase 2 Study of Novel Topical Antifungal for Onychomycosis Demonstrates Efficacy
Anacor Pharmaceuticals announced the end-of-treatment results from a 60-patient, Phase 2, open-label study of 5 percent and 7.5 percent solutions AN2690 in onychomycosis, a fungal infection of the nail and nail bed. At 6 months, halfway through the study, 50 percent of patients in the 7.5 percent group and 45 percent of patients in the 5 percent dose group met the primary endpoint of the study, which was more than 2 mm of clear nail growth and a negative fungal culture.
Subjects were treated once daily with AN2690, a topical antifungal drug, and evaluated for both a clinical response by measuring the length of new clear nail growth as well as for the presence of fungi by culture and direct microscopic evaluation.

VioQuest Pharmaceuticals Doses First Patient in Phase I/IIa Clinical Trial With VQD-001 (Sodium Stibogluconate) for Treatment of Solid Tumors VioQuest Pharmaceuticals, Inc. announced that it has dosed the first patient in its Phase I/IIa clinical trial of VQD-001, Sodium Stibogluconate (SSG), for evaluation of solid tumors, at the MD Anderson Cancer Center. VQD-001 has shown in preclinical studies to specifically inhibit protein tyrosine phosphatases (PTPs), a family of enzymes believed to play a crucial role in solid tumor formation. PTPs are over-expressed in many advanced malignancies, including renal cancer and melanoma. Based on preclinical activity demonstrated in animal models, VQD-001 may represent a novel oncology therapeutic for halting solid tumor growth.
The trial is a Phase I/IIa, open-label, dose escalation study to evaluate the safety, tolerability and pharmacokinetics of VQD-001 in combination with Interferon alpha-2b for patients with advanced malignancies.
Among the goals of this clinical trial is to find the highest tolerable dose of VQD-001 combined with Interferon alfa-2b in the treatment of patients with advanced cancer that have not responded to standard treatment or where there is no standard treatment for that type of cancer. The effectiveness and safety of this drug combination will also be studied.



Corcept Therapeutics Announces Negative Results From the Second of Three Phase 3 Studies Evaluating CORLUX® for Treating the Psychotic Features of Psychotic Major Depression
Corcept Therapeutics Incorporated announced that the second of its three Phase 3 trials evaluating CORLUX for treating the psychotic features of Psychotic Major Depression (PMD) was negative. Study 09 was a randomized, double-blind, placebo-controlled study. The primary endpoint, a responder analysis, was the proportion of patients with at least a 50 percent improvement in the Brief Psychiatric Rating Scale Positive Symptom Subscale (BPRS PSS) at both Day 7 and Day 28. Specifically, the BPRS is an 18-item rating instrument used to assess psychopathology, and the PSS is a subset of four items in the BPRS that specifically measure psychosis. The study revealed no meaningful separation in response between patients receiving CORLUX and patients receiving placebo. The two key secondary endpoints of Study 09 were similarly negative.



Human Genome Sciences Reports Positive Results of Phase 1 Clinical Trial of CCR5 mAb in Patients Infected with HIV-1
Human Genome Sciences, Inc. announced that the results of a Phase 1 clinical trial of HGS004 (CCR5 mAb) demonstrate that it was well tolerated and exhibited antiviral activity in patients who are infected with HIV-1, the retrovirus that causes acquired immunodeficiency syndrome (AIDS). The results were reported in San Francisco in an oral presentation at the American Society for Microbiology's 46th Annual Conference on Antimicrobial Agents and Chemotherapy (ICAAC).
The study demonstrates that HGS004 was well tolerated and exhibited significant dose-related antiviral activity that correlates well with pharmacokinetic data and with the sensitivity of specific HIV-1 viral strains. We note that data from in vitro studies suggest that HGS101, an alternate CCR5 mAb candidate, is likely to have approximately 5.5-fold greater potency and a broader range of activity against HIV-1 viral strains than HGS004. The other attributes of HGS101 are similar to those of HGS004, including favorable pharmacokinetics, strong in vitro evidence of anti-viral activity that is additive or synergistic in combination with other therapeutic agents, and a low likelihood of the development of resistance. In the coming months, we will determine the best path forward for the HGS CCR5 mAb program.



FDA Approves Two New Indications for Rituxan® in Patients With Non-Hodgkin's Lymphoma
Genentech, Inc. and Biogen Idec, Inc. announced that the U.S. Food and Drug Administration (FDA) has approved, after a Priority Review, two additional uses for Rituxan® (Rituximab) for patients with CD20-positive, B-cell non-Hodgkin's lymphoma (NHL). One new indication for Rituxan is for first-line treatment of previously-untreated patients with follicular NHL in combination with CVP (cyclophosphamide, vincristine and prednisolone) chemotherapy. The second new indication is for the treatment of low-grade NHL in patients with stable disease or who achieve a partial or complete response following first-line treatment with CVP chemotherapy.



Final Data From Two Phase II Trials Indicate Activity of Adecatumumab (MT201) in Breast and Prostate Cancer
Micromet, Inc. and Serono reported on the outcome of two phase II trials testing the activity of adecatumumab (MT201) in metastatic breast cancer and in prostate cancer, respectively. Adecatumumab originated at Micromet and is developed in collaboration between Micromet and Serono. The product candidate, a fully human monoclonal antibody targeting tumor cells overexpressing the epithelial cell adhesion molecule (EpCAM), was assessed as a single agent for efficacy and safety in patients with EpCAM-positive metastatic breast cancer (N=109) and in patients with prostate cancer (N=84). The studies tested adecatumumab at two dose levels in patients with high and low EpCAM expression. The results suggested dose dependent activity of adecatumumab as well as a dependency on relevant levels of target expression. Final results from a phase II trial with adecatumumab in metastatic breast cancer were reported at the 31st Congress of the European Society of Medical Oncology (ESMO) in Istanbul, Turkey. This randomized, open label study was conducted in 5 European countries with 26 centers participating. Patients were stratified according to EpCAM expression into two groups, one with low EpCAM expression and another with high level EpCAM expression. Each group was then randomized into two arms treated every two weeks by intravenous infusion at either 2 mg adecatumumab per kg body weight (2 mg/kg) or at 6 mg adecatumumab per kg body weight (6 mg/kg).


Positive Phase I Data On AS1411
Antisoma announced the presentation of positive phase I results for its aptamer drug AS1411. Findings in renal cancer are particularly strong. Antisoma will therefore proceed to a phase II trial in this indication. Antisoma will also initiate a phase II trial in a blood cancer indication. Both trials are expected to start in 2007. The phase I trial of AS1411 initially recruited patients with various cancers. During 2005, it was extended to recruit additional patients with renal and lung cancers. Twelve renal cancer patients were treated. All had advanced, metastatic disease and most had failed prior treatments. Nine (75%) showed clinical benefit, with seven having stable disease for two months or more and two (17%) having objective responses. These are very encouraging results for patients with this stage of disease. Updated details of the two responses are as follows: One patient was enrolled with a 19 cm abdominal tumour, having already been treated in a clinical trial of another drug. He received AS1411 and was reported to show a near-complete response. A recent biopsy has confirmed the disappearance of the abdominal tumour, making this a complete response. The patient has had a single brain metastasis removed surgically and is free of disease over two years after receiving AS1411. A second patient was enrolled with cancer that had spread to both lungs, the liver and lymph nodes, and whose tumours totalled some 20cm in size. He had relapsed after treatment with GemzarTM, IL2 and interferon plus AvastinTM. Following treatment with AS1411, the patient experienced a partial response, with around 70% tumour shrinkage overall at the latest assessment.

Forbes Medi-Tech Announces The Completion Of The US Phase II Trial For Cholesterol-Lowering Drug, FM-VP4
Forbes Medi-Tech Inc. announced the completion of its US Phase II trial for its cholesterol-lowering drug, FM-VP4. The primary efficacy objective of this trial is to determine the effect of two doses of FM-VP4, 450mg and 900mg, given for 12 weeks, compared to placebo, on low density lipoprotein-cholesterol (LDL-C). The goal of this trial is to demonstrate a minimum of 15% reduction from baseline in LDL-C at Week 12. The results are anticipated to be released in mid-to-late fourth quarter 2006.
The multicenter Phase II trial with over 150 male and female mild to moderate hypercholesterolemic subjects was randomized, double-blind and placebo-controlled. Subjects were eligible if they had a LDL-C of 130-210 mg/dL and a triglyceride (TG) level of less than 300 mg/dL. Randomization was equal across three groups with approximately 50 subjects in each group (450mg group, 900mg group and placebo group). In addition to the effects on LDL-C, the effects of FM-VP4 on total cholesterol (TC), high density lipoprotein-cholesterol (HDL-C), HDL:LDL ratio, triglycerides (TG), and C-reactive protein (CRP) will be evaluated in this trial.


FDA APPROVES NEW INDICATION FOR GSK'S LAMICTAL
The FDA has approved a new use of GlaxoSmithKline's (GSK) anti-seizure drug Lamictal (lamotrigine) Tablets for the treatment of one of the most serious forms of epilepsy — primary generalized tonic-clonic (PGTC) seizures, also known as "grand mal" seizures. With this new indication, Lamictal can now be used as add-on therapy to treat PGTC seizures in children ages 2 and older and adults.
This new use marks the fifth FDA approval for Lamictal in epilepsy, making it one of the few antiepileptic drugs with established efficacy in a broad spectrum of seizure types, including partial and generalized seizures. Lamictal is also approved as maintenance therapy for adults with bipolar I disorder.
The approval is based on a multicenter, placebo-controlled trial in pediatric and adult patients. Patients with partial seizures were excluded from this rigorous assessment of Lamictal. In the study, Lamictal was given to patients whose seizures were not well-controlled, even while taking one or two other anti-seizure medications. Lamictal was highly effective in reducing the frequency of PGTC seizures. Over the entire treatment period, Lamictal significantly reduced PGTC seizures by 66 percent compared with 34 percent for the placebo group.


MERCK'S CERVICAL CANCER VACCINE APPROVED IN EUROPE
Merck has announced that the European Commission has approved its cervical cancer vaccine, Gardasil (quadrivalent human papillomavirus recombinant vaccine). Gardasil has been approved as the first and only vaccine in the European Union (EU) for use in children and adolescents ages 9 to 15 and adult females ages 16 to 26 for the prevention of cervical cancer, high-grade cervical dysplasias/precancers, high-grade/precancerous vulvar dysplastic lesions and external genital warts caused by human papillomavirus types 6, 11, 16 and 18.
The vaccine will be marketed by Sanofi Pasteur MSD, a joint venture between Sanofi Pasteur and Merck, in 19 European countries including 15 in the EU. In the remaining countries, the vaccine will be marketed by Merck Sharp & Dohme as either Gardasil or Silgard.
The FDA approved Gardasil on June 8 for girls and women over the age of 9. Gardasil is also approved in Mexico, Australia, Canada, New Zealand, Brazil and some African countries.


ACORDA ANNOUNCES POSITIVE RESULTS FROM MS WALKING STUDY
Acorda Therapeutics has announced positive results from its Phase III trial of Fampridine-SR on multiple sclerosis (MS) patients' ability to walk. Statistical significance was achieved on all three efficacy criteria defined in the Special Protocol Assessment by the FDA. A significantly greater proportion of people taking Fampridine-SR had a consistent improvement in walking speed, the study's primary outcome, compared with people taking placebo (34.8 percent versus 8.3 percent) as measured by the Timed 25-Foot Walk. In addition, the effect was maintained in this study throughout the 14-week treatment period and there was a statistically significant improvement in the 12-Item MS Walking Scale for walking responders versus non-responders.
The average increase in walking speed over the treatment period compared with baseline was 25.2 percent for the drug group versus 4.7 percent for the placebo group. Increased response rate on the Timed 25-Foot Walk was seen across all four major types of MS. In addition, statistically significant increases in leg strength were seen in both the Fampridine-SR Timed Walk responders and the Fampridine-SR Timed Walk non-responders compared with placebo.
The double-blind, placebo-controlled trial was designed to evaluate the safety and efficacy of Fampridine-SR in improving walking ability in people with MS. The trial, which enrolled 301 individuals at 33 MS centers in the United States and Canada, recruited patients between 18 and 70 years old with a definite diagnosis of MS and some degree of walking disability. The study was open to people with all types of MS, including primary-progressive, secondary-progressive, relapsing-remitting and progressive-relapsing. Participants were permitted to remain on a stable regimen of their current medications, including interferons. Secondary endpoints for the trial included measurements of leg strength.

FDA APPROVES AMGEN'S VECTIBIX FOR COLORECTAL CANCER
The FDA has approved Amgen's Vectibix (panitumumab) for the treatment of metastasized colorectal cancer following standard chemotherapy. Vectibix, a monoclonal antibody that binds to a protein called epidermal growth factor receptor (EGFR) on some cancer cells, received an accelerated approval after showing effectiveness in slowing tumor growth and, in some cases, reducing the size of the tumor.
The FDA approved Vectibix on the basis of the results of a randomized, controlled clinical trial of 463 patients with metastatic cancer of the colon and the rectum after undergoing treatment with chemotherapy drugs fluoropyrimidine, oxaliplatin and irinotecan.
The mean time to disease progression or death in patients receiving Vectibix was 96 days versus 60 days in patients receiving the best standard supportive care. In addition, 8 percent of the patients on Vectibix experienced a tumor shrinkage that in some cases exceeded 50 percent of the pretreatment size of the tumor. Both study groups showed similar overall survival.
Under the accelerated approval program, drugs for serious and life-threatening diseases can be made available earlier in the development process if a promising effect of the drug is observed. As part of the approval, Amgen committed to conduct a postmarketing trial to show whether the drug improves patients' survival in patients with less prior chemotherapy.


CENTOCOR'S REMICADE APPROVED FOR PLAQUE PSORIASIS
Centocor announced that the FDA has approved Remicade (infliximab) for the treatment of adult patients with chronic severe plaque psoriasis who are candidates for systemic therapy and when other systemic therapies are medically less appropriate. The recommended dose is an infusion of 5 mg/kg followed by additional doses at two and six weeks after the first infusion and then every eight weeks thereafter.
Data from two multicenter, randomized, double-blind, placebo-controlled trials served as the primary basis for approval. In the Phase III clinical trial EXPRESS, eight out of 10 patients receiving Remicade 5 mg/kg induction therapy achieved 75 percent improvement in psoriasis as measured by Psoriasis Area Severity Index (PASI) by week 10. Similar results were seen with EXPRESS II, the second Phase III study. The majority of patients who continued on this regimen achieved PASI 75 at week 50, the last visit in both studies. More than 1,200 patients participated in the two trials.