Pipeline Series Oct 9 till Oct 16, 2006

Phase I

Ceregene Announces Promising Phase 1 Results From Gene Therapy Trial for Parkinson's Disease
Ceregene, Inc. announced that CERE-120, a gene therapy product in development for the treatment of Parkinson's disease, was well tolerated and appeared to reduce symptoms by approximately 40% (p<0.001), as measured by the Unified Parkinson's Disease Rating Scale (UPDRS) motor "off" score, in an open-label Phase 1 study in 12 patients with advanced disease. Initial results of the study were presented by William J. Marks Jr., M.D., principal investigator of the study and associate professor of Neurology at the University of California, San Francisco (UCSF) at the American Neurological Association annual meeting in Chicago.
The study was supported in part by a grant from The Michael J. Fox Foundation for Parkinson's Research. Based on the initial results, the Foundation announced plans to partially fund a Phase 2 study with a $1.9 million grant.



Cerus Initiates Phase I Clinical Trial for CRS-100
Cerus Corporation announced that the first patient has been dosed in a Phase I clinical trial of CRS-100, the company's lead immunotherapy product. The primary objectives of the study are to determine the maximum tolerated dose and to explore the safety profile of a single dose of CRS-100 in adult patients with cancer that has metastasized to the liver.
CRS-100 is a proprietary attenuated strain of Listeria monocytogenes that has been designed by Cerus to increase safety margins while preserving its potential to trigger a powerful immune response.
The multi-center, open-label, single-injection, dose escalation clinical trial is designed to explore safety and tolerability of CRS-100 in volunteer patients who have carcinoma, refractory to standard treatment (or for whom no standard treatment is available), and who additionally have liver metastases. The trial is currently being conducted at two centers in the United States.



Alnylam Initiates Phase I Clinical Study of Inhaled Formulation of ALN-RSV01, an RNAi Therapeutic for the Treatment of Respiratory Syncytial Virus (RSV) Infection
Alnylam Pharmaceuticals, Inc. announced that it has initiated a Phase I human clinical trial of an inhaled formulation of ALN-RSV01 in the U.S. to evaluate its safety, tolerability, and pharmacokinetics in healthy adult volunteers. The inhaled formulation of ALN-RSV01 used in this Phase I study is a nebulized formulation, and advances previous clinical work for ALN-RSV01 administered as an intranasal spray. ALN-RSV01, an un-partnered Alnylam program, is an RNAi therapeutic in clinical development for the treatment of respiratory syncytial virus (RSV) infection.
Alnylam previously completed two Phase I human clinical trials of ALN-RSV01 using an intranasal formulation. The previous studies demonstrated that ALN-RSV01 was safe and well tolerated when administered intranasally in relevant doses to human volunteers and had a profile comparable to placebo. This newly initiated Phase I trial with inhaled ALN-RSV01 uses a formulation that is designed to deliver the RNAi therapeutic to the lungs, and is the expected formulation for the treatment of RSV in naturally infected patients. Models of this aerosolized formulation of ALN-RSV01 predict that it can be delivered to the alveoli and the small airways of the infant and adult human lung.



COUGAR BIOTECH RELEASES DATA ON PROSTATE CANCER DRUG
Cougar Biotechnology has announced positive Phase I data on the company's prostate cancer drug CB7630 (abiraterone acetate). In the trial, CB7630 was administered once daily to chemotherapy-naive patients with CRPC, who had progressive disease despite treatment with LHRH analogues and multiple other hormonal therapies including antiandrogens, diethylstilboestrol and dexamethasone.
The results from the trial showed that in the 14 patients tested, CB7630 was well-tolerated at doses as high as 2,000 mg/day with minimal toxicity. Moreover, no dose-limiting toxicity has been observed in the trial to date. Of the 12 patients that were evaluable for antitumor activity, eight patients (67 percent) experienced a confirmed decline in prostate specific antigen (PSA) levels of greater than 50 percent and six patients (50 percent) experienced PSA declines of greater than 90 percent. Of the five evaluable patients with measurable tumor lesions, treatment with CB7630 resulted in partial radiological responses (as measured by the RECIST criteria) in three (60 percent) patients. Individual patients treated with CB7630 also experienced radiographic regression of bone metastases and improvement in pain.
Circulating tumor cells (CTC) were detected in six of 14 patients, and changes in CTC counts were shown to correlate with changes in PSA. Ten (71 percent) of the 14 patients will continue on treatment with CB7630, with some patients having been on the drug for more than nine months.



Medarex and PharmAthene Announce Phase I Results of Anthrax Therapeutic Valortim™Medarex, Inc. and PharmAthene, Inc. announced Phase I study results for Valortim™ (MDX-1303) in healthy volunteers. Valortim is a fully human antibody against anthrax infection developed using Medarex's UltiMAb Human Antibody Development System®. The study results were presented in an oral presentation on Sunday, October 15, 2006, at the Infectious Diseases Society of America (IDSA) annual meeting held in Toronto, Canada. The presentation abstract is posted on the IDSA web site
A Phase I clinical study was conducted to assess the safety and tolerability of Valortim. Forty-six healthy volunteers received either a single intravenous (IV) dose of Valortim ranging from 0.3 to 20.0 mg/kg (10 subjects in cohorts receiving 1.0, 3.0 or 10.0 mg/kg and 3 subjects in cohorts receiving 0.3 and 20 mg/kg) or a single 100 mg intramuscular (IM) dose of Valortim (10 subjects).
The Phase I data showed that Valortim was safe and well tolerated. No drug-related Grade 2-4 or serious adverse events were reported. Grade 1 adverse events were reported in 16 of the volunteers overall, with the most common being pain/burning at the injection site for those being dosed intramuscularly (6 subjects). There were also a few mild headaches (3 subjects overall). Initial analyses of serum pharmacokinetics revealed increasing peak concentrations and overall duration of exposure to antibody with increasing dose, and a half-life of approximately 26 days for IV administration, and approximately 32 days for IM dosing. In the cohorts dosed with 1.0 mg/kg IV or 100 mg IM, individual subjects were tested for the level of toxin neutralizing activity present in their serum 71 days after dosing. The level of activity was comparable to the level of toxin neutralizing activity seen in pooled human sera provided by the CDC; these reference sera were generated from anthrax toxin immunized individuals, and provide a standard for defining a protective vaccine response. These data suggest that a single dose of Valortim given by the convenient intramuscular route of administration could provide protection for two months, comparable to that present in previously immunized individuals. Exposed but unvaccinated individuals are typically prescribed a two-month course of antibiotic prophylaxis to assure protection in the absence of prior protective antibodies.



GENTA BEGINS STUDY OF DRUG THAT TARGETS THE C-MYB ONCOGENE
Genta has announced initiation of a Phase I clinical trial using a new anticancer drug derived from the company's DNA/RNA medicines program. The new compound, known as G4460, uses antisense technology to target an oncogene known as c-myb that regulates key functions in cancer cells. Using an accelerated dosing schedule, this study will evaluate dosing regimens, safety, biologic activity and down-regulation of c-myb in patients with advanced hematologic cancers. G4460 has been granted orphan drug designation by the FDA for treatment of patients with chronic myelocytic leukemia.
Genta's DNA/RNA medicines program uses drugs that are based on chemical modifications of DNA or RNA to selectively knock out the function of genes that may be involved in the cause or progression of cancer. G4460 targets an oncogene product known as c-myb, which is a protein that directly binds to cellular DNA. C-myb is believed to regulate the expression of other genes that are involved in the growth and differentiation of cancer cells. Over-expression of c-myb blocks differentiation, promotes proliferation and decreases apoptosis.
Potential clinical targets for G4460 include chronic myelocytic leukemia, melanoma, neuroblastoma and cancers of the breast, pancreas and colon. Genta has licensed key patents and technology related to the composition and human use of G4460.




Phase II

Inspire Begins Phase 2 Clinical Program of Epinastine for Seasonal Allergic Rhinitis
Inspire Pharmaceuticals, Inc. announced that an investigational new drug application (IND) for epinastine nasal spray has been filed with the U.S. Food and Drug Administration (FDA) and is in effect, having passed the 30-day review period. Inspire previously acquired certain exclusive rights from Boehringer Ingelheim to develop and market an intranasal dosage form of epinastine in the United States and Canada for the treatment or prevention of rhinitis.
Inspire has begun Phase 2 clinical testing in patients with seasonal allergic rhinitis, based on the existing data package on epinastine, including Phase 1 safety data. The Phase 2 program will include clinical and toxicology studies to determine the optimal formulation and dose. The initial clinical trial compares several formulations and concentrations over one day.



GENASIS Phase IIb Trial Didn't Meet Primary Endpoint
Corautus Genetics Inc. said its Genasis Phase IIb clinical trial for treatment of severe angina didn't achieve a statistically significant difference from placebo for the primary endpoint.
The Atlanta biopharmaceutical company was looking for improvement of at least one minute in exercise tolerance time from baseline to three months.
Corautus has been developing a gene-therapy product candidate using the VEGF-2 gene, a naturally occurring growth factor believed to promote the development of supplemental collateral blood vessels to prevent angina.
Corautus said Genasis treated 295 patients with Class III or IV angina that weren't suitable candidates for traditional revascularization procedures.
Corautus said "the placebo effect was much more significant and was sustained longer than was anticipated in the design of the Genasis trial."
Corautus said "there was no significant separation from the placebo in any active dose group."



Roche Advances Oral Polymerase Inhibitor into Phase II Study in Patients with Chronic Hepatitis C
Roche announced the initiation of the first Phase II study to evaluate R1626, an investigational polymerase inhibitor, for the treatment of chronic hepatitis C. The drug has also been granted Fast Track designation by the U.S. Food and Drug Administration (FDA), a program designed to facilitate the development and to expedite the review of new drugs with the potential to help treat serious or life-threatening conditions.
R1626, which has been shown to have a strong antiviral effect, uses a different mechanism of action from the current standard HCV treatment. In a Phase I study, the drug achieved significant reductions in viral levels in chronic hepatitis C patients infected with genotype 1, the most difficult to treat form of the virus. While patients with genotype 1 virus in clinical trials with Roche's currently-available hepatitis C therapies, PEGASYS® (peginterferon alfa-2a) and COPEGUS (ribavirin), had an approximate 50 percent chance of achieving a sustained virologic response (SVR).

By moving R1626 into its first Phase II trial, Roche signifies its commitment to improving therapeutic options for patients with hepatitis C. The trial will evaluate the safety and antiviral effect of R1626 in combination with PEGASYS and COPEGUS.



Biovitrum Initiates Clinical Phase II Study of Glaucoma Treatment
The biopharma company Biovitrum has initiated a clinical Phase II study with the candidate drug BVT.28949, a 5-HT2A antagonist for the treatment glaucoma. The results are expected to be available midyear of 2007.
The first clinical safety study included 64 healthy volunteers and was entered in September 2005. This study has been compiled and evaluated and convincing positive results support continued clinical trials.
The present Phase II study includes 150 patients with an elevated intraocular pressure (a hallmark of glaucoma) and the study is estimated to be completed during spring 2007 with results available in the middle of the year. The Phase II study is placebo-controlled (results are compared to patients treated with a preparation without real pharmacological effect), and is carried out at several clinics in both Sweden and Ukraine.



TorreyPines Therapeutics Initiates Phase IIb Clinical Trial in Acute Migraine for Lead Compound Tezampanel
TorreyPines Therapeutics, Inc. announced the initiation of a Phase IIb clinical trial for its lead product candidate, tezampanel, a novel pain compound in development for the treatment of acute migraine. An AMPA/kainate (AK) receptor antagonist, tezampanel offers a non-narcotic, non-vascular approach to the management of headache pain and represents a potentially promising alternative to current migraine treatments.
The double-blind, placebo-controlled, parallel-group study will enroll approximately 300 patients and treat a single migraine attack, with or without aura. Equal numbers of patients will be randomized to one of four arms and receive a 40 mg, 70 mg, or 100 mg single subcutaneous dose of tezampanel or placebo. The primary efficacy endpoint is headache pain relief at two hours post-dose. Secondary efficacy endpoints include pain free at two hours, sustained pain relief and sustained pain free at 24 hours, and headache recurrence and relapse. Additional measures include assessments of functional disability and patient satisfaction, relief of migraine-associated symptoms such as nausea, vomiting, photophobia (sensitivity to light) and phonophobia (sensitivity to sound), as well as various assessments that characterize speed of onset. Safety, tolerability and pharmacokinetics will also be evaluated. The study will be conducted in approximately 25 centers in the U.S.





Phase III

Cobalis Completes Patient Dosing in Phase III Clinical Trials for OTC Anti-Allergy Product Candidate
Cobalis Corp. announced that the Company has completed the dosing portion of its ten-week twin Phase III Clinical Trials for its anti-allergy medication, PreHistin™. The randomized, double blind, placebo-controlled trials are designed to test the safety and efficacy of pre-seasonal treatment with PreHistin on moderate to moderately severe seasonal ragweed allergy patients.
The Phase III Clinical Trials involved 1,551 patients at 23 sites across the central, southern and eastern United States who received either placebo or a 3.3 mg sublingual dosage of PreHistin twice daily for three weeks prior to the onset of the ragweed allergy season and for an additional three weeks into the allergy season. Symptom diaries are being maintained for an additional four weeks following treatment to determine duration of effect. Cobalis anticipates reporting top-line efficacy results from the pivotal trials in the first quarter of 2007.
The objective of the twin Phase III pivotal trials is to provide the FDA with sufficient safety and efficacy data to support marketing approval of PreHistin. The primary efficacy parameter for each trial is the difference in the mean reduction in Total Nasal Symptom Score (TNSS) observed between placebo and PreHistin over weeks four, five and six of the studies.



OMRIX Biopharmaceuticals Announces Positive Phase 3 Clinical Trial Results for Human Thrombin
OMRIX Biopharmaceuticals, Inc. announced positive results from its Phase 3 pivotal clinical trial of human thrombin in achieving hemostasis in general surgery procedures. The non-inferiority clinical trial evaluated the equivalence of topical human thrombin to bovine thrombin in terms of safety and efficacy. All primary endpoints were met.
The pivotal, multi-center, prospective, randomized, controlled, double-blinded Phase 3 clinical trial was conducted at 22 sites in the U.S. in subjects undergoing elective surgical procedures, including: cardiovascular surgery, neurologic (spine) procedures, and general surgery or post-traumatic procedures. 305 patients were randomized at a 1:1 ratio to receive either human thrombin, the investigational product or bovine thrombin, the control. Approximately half (153) of the patients received human thrombin. Enrollment of subjects by specialty included: 93 subjects in cardiovascular surgery, 121 subjects in neurologic (spine) procedures, and 91 subjects in general surgery or post-traumatic procedures. The study was designed to support broad product labeling for the use of thrombin as an aid to control bleeding during surgery.




Submissions

GlaxoSmithKline submits supplemental drug application in the USA for Advair in COPD
GlaxoSmithKline announced that it has submitted a supplemental new drug application to the FDA to expand labeling for Advair Diskus® (fluticasone propionate and salmeterol inhalation powder) in the USA based on results from TORCH, a three year study that showed a reduction in the risk of death and the rate of COPD exacerbations, and other supporting studies.
COPD, or chronic obstructive pulmonary disease, is a complex lung disease that results in a progressive decline in lung function that is ultimately debilitating and life-threatening. It is the 4th leading cause of death in the U.S.
Results of the TORCH study (TOwards a Revolution in COPD Health) showed a 17.5% reduction in risk of death from any cause over three years for patients receiving Advair 500/50 as compared with patients on placebo (p=0.052). Advair also reduced the rate of COPD exacerbations by 25% compared with placebo (p<0.001). Quality of life, as measured by the St George’s Respiratory Questionnaire (SGRQ), was improved by Advair 500/50 when compared to placebo (p<0.001) although it did not meet the predefined magnitude of difference. In the study, Advair was associated with increased reporting of pneumonia when compared with placebo (p<0.001). Other adverse events (e.g. candidiasis, dysphonia, contusion) generally appear consistent with those seen in previous studies of Advair in patients with COPD.
Advair 250/50 is currently indicated for the maintenance treatment of airflow obstruction in patients with COPD associated with chronic bronchitis. The supplemental drug application seeks marketing approval for Advair 500/50 and expanded labeling based on data from TORCH and other supporting studies.


Solvay Pharmaceuticals and Wyeth Announce Submission of New Drug Application for Bifeprunox to Treat Schizophrenia
Solvay Pharmaceuticals, Inc. and Wyeth Pharmaceuticals announced that a New Drug Application (NDA) was submitted to the U.S. Food and Drug Administration (FDA) for bifeprunox, an investigational atypical antipsychotic for the treatment of schizophrenia.
The NDA submission is based on safety and efficacy studies that evaluated bifeprunox for the treatment of schizophrenia in approximately 2,550 patients. Patients were evaluated with acute exacerbations for six weeks, and stable patients were evaluated for six months.



Indevus Announces Submission of New Drug Application Seeking Approval for SANCTURA XR to Treat Overactive Bladder
Indevus Pharmaceuticals, Inc. announced that it has submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) seeking approval for SANCTURA XR™ to treat patients with overactive bladder. SANCTURA XR is the once-daily formulation of SANCTURA® (trospium chloride), which is currently marketed for overactive bladder.
The NDA submission follows the June and July 2006 announcements of positive results from two Phase III trials conducted for SANCTURA XR in overactive bladder. Both trials met their primary endpoints and key secondary endpoints. In addition, the Company believes that SANCTURA XR has set a new tolerability benchmark for oral drugs in the treatment of overactive bladder with an overall dry mouth incidence of 10.7% in the Phase III trials.
The NDA includes the results of the Company's Phase III clinical program as well as the results of additional Phase I and Phase II studies. The previous NDA for SANCTURA is also referenced for supportive data.



EPICEPT FILES FOR APPROVAL OF LEUKEMIA DRUG IN EUROPE
EpiCept announced it has submitted a marketing authorization application (MAA) to the European Medicines Agency (EMEA) for Ceplene (histamine dihydrochloride), the company's lead oncology product candidate, administered in conjunction with interleukin-2 (IL-2), for the maintenance of first remission in patients with acute myeloid leukemia (AML).
The MAA submission for Ceplene will be reviewed under the EU centralized procedure, and if approved would provide a marketing authorization valid in all EU member states. The European Commission has previously granted orphan drug status to Ceplene for use in the treatment of AML.
The pivotal efficacy and safety data for this MAA submission is from a Phase III clinical trial for Ceplene in conjunction with interleukin-2. This study met its primary endpoint of preventing relapse as shown by increased leukemia-free survival for AML patients in remission. The study was conducted in 11 countries and included 320 randomized patients. The data demonstrated that patients with AML in complete remission who received 18 months of treatment with Ceplene plus low-dose interleukin-2 experienced a significantly improved leukemia-free survival compared with the current standard of care, which is no treatment after successful induction of remission.




Approvals

FDA Approves Avastin® in Combination With Chemotherapy for First-Line Treatment of Most Common Type of Lung Cancer
Genentech, Inc. announced that the U.S. Food and Drug Administration (FDA) has approved Avastin® (bevacizumab) to be used in combination with carboplatin and paclitaxel chemotherapy for the first-line treatment of patients with unresectable, locally advanced, recurrent or metastatic non- squamous, non-small cell lung cancer (NSCLC), the most common type of lung cancer. The approval is based on a Phase III study (E4599) that showed Avastin in combination with chemotherapy resulted in a 25 percent improvement in overall survival compared to chemotherapy alone (based on a hazard ratio of 0.80).
The FDA approval for this new indication was based on results from E4599, a randomized, controlled, multi-center trial that enrolled 878 patients with unresectable, locally advanced, recurrent or metastatic non-squamous NSCLC. Patients with mixed histology were excluded if the predominant cell type was squamous. Results showed that patients receiving Avastin plus paclitaxel and carboplatin chemotherapy had a 25 percent improvement in overall survival, the trial's primary endpoint, compared to patients who received paclitaxel and carboplatin alone (based on a hazard ratio of 0.80). One-year survival was 51 percent in the Avastin plus chemotherapy arm versus 44 percent in the chemotherapy-alone arm. Median survival of patients treated with Avastin plus chemotherapy was 12.3 months, compared to 10.3 months for patients treated with chemotherapy alone.



FDA Approves NEXIUM for the Treatment of Zollinger-Ellison Syndrome
AstraZeneca announced that the US Food and Drug Administration (FDA) has approved a new indication for the prescription proton pump inhibitor NEXIUM® (esomeprazole magnesium) for the treatment of Zollinger-Ellison Syndrome (ZES). NEXIUM already is indicated for the treatment of gastroesophageal reflux disease (GERD) in adults and children ages 12 to 17, and to reduce the risk of NSAID-associated gastric ulcers in at-risk patients.
ZES is a rare but serious chronic condition characterized by the development of tumors that secrete excessive levels of gastrin, a hormone that stimulates acid production by the stomach.
The new indication for NEXIUM is based on clinical data in which twenty- one patients received one of several doses of NEXIUM, depending on their symptoms and the degree of their acid output. The twelve-month, open-label trial demonstrated that NEXIUM effectively maintains basal acid output control in this patient population. NEXIUM® (esomeprazole magnesium) was well tolerated throughout the trial.



U.S. Food and Drug Administration Approves ARICEPT® for Treatment of Severe Alzheimer's Disease
Eisai and Pfizer Inc announced that the U.S. Food and Drug Administration (FDA) has approved a supplemental New Drug Application (sNDA) for ARICEPT® (donepezil HCl tablets) for treatment of severe Alzheimer's disease (AD). The application was submitted by Eisai Medical Research Inc. on behalf of Eisai Co., Ltd. and Eisai Inc.
With this approval, ARICEPT becomes the first and only prescription medication to treat the full spectrum of AD (mild, moderate and severe). ARICEPT, which is co-promoted in the United States by Eisai Inc. and Pfizer Inc, has been approved in the United States since 1996 for treatment of mild to moderate AD.

The approval was based on results of a pivotal six-month, multi-center, randomized, double-blind, placebo-controlled clinical trial involving 248 Swedish nursing home patients with severe AD (Mini Mental State Exam scores 1-10). The study, the first to evaluate ARICEPT® (donepezil HCl tablets) 10 mg once-daily exclusively in patients with severe AD, was published March 2006 in The Lancet. Patients treated with ARICEPT had statistically significant benefit compared to those taking placebo in both primary efficacy measures: the Severe Impairment Battery for cognition and the Modified Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory for Severe Alzheimer's Disease for function/activities of daily living. Treatment with ARICEPT was generally well tolerated. The most commonly reported adverse events in ARICEPT-treated patients that occurred at a frequency of at least 5 percent and at twice the rate of placebo-treated patients, were diarrhea, anorexia, vomiting, nausea and bruising.