Depomed, Inc. (NASDAQ:DEPO) announced that it has completed enrollment of the Phase 3 clinical trial of DM-1796 for the treatment of post-herpetic neuralgia.

“We are glad that we successfully arrived at another milestone that brings Depomed closer to potential milestone payments related to the development of DM-1796 and further royalties and sales milestones upon its approval. We remain excited to have Solvay Pharmaceuticals as a strong and committed partner in the neuroscience field, we share with their expectation that DM-1796 could become a significant product for the treatment of neuropathic pain,” said Carl A. Pelzel, Depomed’s president and chief executive officer. Dr. Michael Sweeney, Depomed’s vice president, Research and Development, added, ” I would like to thank all clinical investigators, patients, and Depomed employees whose dedication to DM-1796 enabled us to complete enrollment as planned. We look forward to the top-line results of the trial in the fourth quarter of this year.”

Clinical Development Status

In March 2008, Depomed initiated dosing of the first patient in this Phase 3 clinical trial for DM-1796 for PHN. The study is a randomized, double-blind, placebo-controlled study of approximately 450 PHN patients. Patients in the study are randomized into two treatment arms: placebo, or 1800mg of DM-1796 dosed once daily.

Postherpetic Neuralgia (PHN)

Postherpetic neuralgia (PHN) is a persistent neuropathic pain condition. It is caused by nerve damage after a shingles, or herpes zoster, viral infection and afflicts approximately one in five patients diagnosed with shingles (~ 150,000 individuals) in the U.S. The incidence of PHN increases in elderly patients, with 75 percent of those over 70 years old who have shingles developing PHN. The pain associated with PHN reportedly can be so severe that some patients are unable to resume normal activities for months.

Leveraging Depomed’s Gastric Retentive Technology

Gabapentin available on the market today is formulated for immediate release (IR). Upon ingestion, the entire administered dose is released into the stomach allowing for it to be rapidly absorbed into the blood. This rapid absorption leads to peak concentrations of the active ingredient, which gives rise to commonly experienced side effects including dizziness and daytime sleepiness. Patients taking immediate release formulations of gabapentin frequently need to take it three to four times a day to effectively manage their pain.

Formulated with gastric retentive technology, DM-1796 is designed for targeted, controlled release to the upper GI tract over a six to eight hour period. This extended release allows for the drug to be gradually absorbed into the blood, reducing the likelihood of peak concentrations and potentially resulting in fewer side effects than seen with immediate release formulations. Greater treatment tolerability and a more convenient dosing regimen made possible with this technology could potentially translate into greater patient compliance and ultimately better pain management.

About Depomed

Depomed, Inc. is a specialty pharmaceutical company with two product candidates in Phase 3 clinical development, two approved products on the market and other product candidates in its early stage pipeline. Product candidate DM-1796 is in Phase 3 clinical development for the treatment of neuropathic pain and has been licensed to Solvay Pharmaceuticals. Product candidate SeradaTM is in Phase 3 clinical development for menopausal hot flashes. GLUMETZA® (metformin hydrochloride extended release tablets) is approved for use in adults with type 2 diabetes and promoted by Santarus, Inc. in the United States. Proquin® XR (ciprofloxacin hydrochloride) is approved in the United States for the once-daily treatment of uncomplicated urinary tract infections. Depomed formulates its products and product candidates with its proven, proprietary Acuform® drug delivery technology, which is designed to improve existing oral medications, allowing for extended, controlled release of medications to the upper gastrointestinal tract. Benefits of Acuform-enhanced pharmaceuticals include the convenience of once-daily administration, improved treatment tolerability and enhanced compliance and efficacy. Additional information about Depomed may be found on its website, www.depomed.com.

Source
Solvay Pharmaceuticals, Inc.

Cougar Biotechnology, Inc. (NASDAQ:CGRB) announced that results from ongoing Phase II clinical trials of Cougar’s investigational drug CB7630 (abiraterone acetate) were presented at the 2009 ASCO Annual Meeting that is currently taking place in Orlando, Florida. The data were released today in three poster presentations. These presentations are further detailed below:

Preliminary results of a phase II multicenter study of chemotherapy-naïve castration-resistant prostate cancer (CRPC) patients not exposed to ketoconazole, treated with abiraterone acetate plus prednisone (COU-AA-002)

A Phase II clinical trial of CB7630 (COU-AA-002) is being conducted by The Prostate Cancer Clinical Trials Consortium, a national clinical research group sponsored by the Department of Defense, with Dr. Charles J. Ryan, Associate Professor of Clinical Medicine at the University of California, San Francisco Comprehensive Cancer Center, as the principal investigator. In this Phase II trial, CB7630 in combination with prednisone is administered once daily to chemotherapy-naïve, ketoconazole-naïve patients with castration-resistant prostate cancer (CRPC), who had progressive disease despite treatment with LHRH analogues and other hormonal therapies.

In his poster discussion presentation, Dr. Ryan presented data on the 33 evaluable patients treated in the trial. After 12 weeks of treatment, 26 patients (79%) experienced a decline in prostate specific antigen (PSA) levels of greater than 30%, 24 (73%) experienced a PSA decline of greater than 50% and 10 (30%) experienced PSA declines of greater than 90%. For the 33 evaluable patients, the median time to PSA progression was 337 days (48 weeks).

Of the 33 evaluable patients, treatment with CB7630 plus prednisone resulted in radiologic disease control in 28 patients (85%) with partial responses in 9 patients (27%) and stable disease in 19 patients (58%).

A multicenter phase II study of abiraterone acetate (AA) demonstrates anti-tumor activity in docetaxel pre-treated castration-resistant prostate cancer (CRPC) patients (COU-AA-003)

The COU-AA-003 Phase II trial of CB7630 in patients with advanced prostate cancer who have failed docetaxel-based chemotherapy was conducted at numerous locations in the United States and United Kingdom. In the trial, CB7630 is administered orally, once daily, to patients with CRPC who have failed treatment with androgen deprivation therapy and failed treatment with first-line docetaxel-based chemotherapy.

Dr. Allison Reid from The Institute of Cancer Research and The Royal Marsden Hospital in the United Kingdom presented data on the 47 patients enrolled in this Phase II trial. CB7630 was well tolerated with only minimal toxicity in this post-docetaxel population. After 12 weeks of treatment, of the 47 patients treated, 24 patients (51%) experienced a decline in PSA of greater than 30%, with 19 patients (40%) demonstrating a decline in PSA levels of greater than 50%, and 6 patients (13%) demonstrating a decline in PSA levels of greater than 90%. Of the 47 evaluable patients with measurable tumor lesions, radiologic disease control was observed in 31 of the 47 patients (66%) with 6 patients (13%) experiencing confirmed partial radiological responses and 25 patients (53%) experiencing stable disease. The median time to PSA progression for the 47 patients in the trial was estimated to be 169 days (24 weeks).

Phase II multicenter study of abiraterone acetate (AA) plus prednisone therapy in docetaxel treated castration-resistant prostate cancer (CRPC) patients: impact of prior ketoconazole (COU-AA-004)

During his poster discussion presentation, Dr. Daniel Danila from Memorial Sloan-Kettering Cancer Center presented data from the ongoing Phase II trial of CB7630 in combination with prednisone in patients with advanced prostate cancer who have failed androgen deprivation and docetaxel-based chemotherapy (COU-AA-004).

The COU-AA-004 Phase II trial is being conducted at numerous locations in the United States and United Kingdom. In the trial, CB7630 in combination with prednisone is administered orally, once daily, to patients with CRPC who have failed treatment with androgen deprivation therapy and have failed treatment with first-line docetaxel-based chemotherapy. To date, a total of 58 patients have been enrolled in the trial at 8 different centers.

Of the 58 patients, 13 patients (22%) had visceral disease, 26 patients (45%) had bone and soft tissue metastases, 11 patients (19%) had bone metastases only and 8 patients (14%) had soft tissue metastases only. Additionally, 27 patients (47%) had been previously treated with ketoconazole, a drug that is currently used off-label as a secondary hormonal therapy.

The combination of CB7630 plus prednisone was well tolerated with only minimal toxicity in this post-docetaxel population. After 12 weeks of treatment, 20 patients (34%) experienced a confirmed decline in PSA levels of greater than 50%. Of the 31 patients who had not received prior treatment with ketoconazole, 13 patients (42%) experienced a confirmed decline in PSA levels of greater than 50%. Furthermore, of the 27 patients who had been previously treated with ketoconazole, 7 patients (26%) experienced a confirmed decline in PSA levels of greater than 50%.

Of the 18 evaluable patients with measurable tumor lesions, 3 patients (17%) experienced confirmed partial radiological responses (as measured by the RECIST criteria) and 11 patients (61%) experienced ongoing stable disease. For the 31 patients who had not received prior treatment with ketoconazole, the median time to PSA progression was estimated to be 198 days (28 weeks). Furthermore, for the 27 patients who had been previously treated with ketoconazole, the median time to PSA progression was estimated to be 99 days (14 weeks).

Alan H. Auerbach, Chief Executive Officer and President of Cougar Biotechnology, said, “We are pleased to present data from these clinical trials at the ASCO Annual Meeting. CB7630 continues to show strong evidence of antitumor activity in patients with chemotherapy-naïve disease as well as in patients with chemotherapy-refractory disease. These populations not only represent significant unmet medical needs in prostate cancer but also are representative of the patient populations being studied in our ongoing Phase III trials (COU-AA-301 and COU-AA-302).”

Arturo Molina, M.D., M.S., FACP, Chief Medical Officer and Executive Vice President of Clinical Research and Development of Cougar, added, “We are pleased to present the multi-center results of these Phase II studies, which continue to support the potential roles of CB7630 both as a second-line hormonal therapy for patients with advanced prostate cancer who fail first-line hormonal treatment and as a second-line therapy for patients with advanced prostate cancer who fail docetaxel-based chemotherapy. These patient groups continue to represent patient populations that are underserved with current treatments.”

Source
Cougar Biotechnology, Inc.

Exelixis, Inc. (Nasdaq:EXEL) and Bristol-Myers Squibb Company (NYSE:BMY) reported encouraging data from an ongoing phase 2 trial of XL184 in patients with previously treated glioblastoma multiforme (GBM) (study XL184-201).

XL184 is an orally administered small molecule inhibitor of receptor tyrosine kinases including MET, VEGFR2, and RET. Overexpression of MET and VEGFR2, as well as the ligands which activate these receptors, has been shown to correlate with poor prognosis in GBM, which is the most common and aggressive form of brain tumor. In addition, phosphorylated RET has been described in some cases of GBM.

Exelixis is co-developing XL184 with Bristol-Myers Squibb Company. John De Groot, MD, of The MD Anderson Cancer Center, and an investigator on the Phase 2 GBM trial, will present the data in a poster session (Abstract #2047) from 8 a.m. to 12 p.m. local time on Sunday, May 31, 2009, at the American Society of Clinical Oncology (ASCO) Annual Meeting, which is being held May 29-June 2 in Orlando.

The exploratory study is evaluating the safety, tolerability and clinical activity of XL184 at a continuous daily dose of 175 mg in patients with previously treated GBM. To date, 46 patients who make up the intent to treat (ITT) population have been enrolled in the trial, including 30 (65%) in first relapse and 16 (35%) in second or third relapse. Importantly, the trial did not exclude patients previously treated with an antiangiogenic agent.

Tumor response, as determined by an independent radiology facility (IRF), using MacDonald criteria were reported. By ITT analysis, 7 of 35 (20%) of the antiangiogenic naïve patients had a confirmed partial response. The overall rate of response in all patients, including the refractory population of previously treated patients with an antiangiogenic therapy, was 15%. The median duration of response by IRF was 2.9 months (range = 1.9-8.6 months). In an exploratory analysis, among 35 patients with at least one post baseline MRI scan, 12 (34%) had tumor shrinkage ?50% as their best response as determined by investigator, including 1 patient who had received prior antiangiogenic therapy.

The efficacy evaluable population was defined as patients having received at least 1 dose of XL184 and either had at least 1 post-baseline tumor assessment per investigator or failed to return for any tumor assessments because of death or clinical determination of progression. In the anti-angiogenic naïve population, 7 of 31 (23%) of efficacy evaluable patients had a confirmed partial response by IRF. The 6-month progression-free survival (PFS) rate in patients receiving no prior antiangiogenic therapy was 23%, with 10 patients censored for PFS at the time of analysis, and the median PFS interval was 3.6 months.

“These initial data from our ongoing GBM program are encouraging, and suggest that XL184 could have utility in this underserved indication,” said Michael M. Morrissey, Ph.D., president of research and development at Exelixis. “We believe that these data support continued evaluation of XL184 in patients with GBM, and we intend to enroll additional patients in this study to better assess the compound’s anti-tumor activity and safety profile in this difficult to treat patient population.”

All 46 patients were evaluated for safety. Most adverse events were of Grade 1 or 2 severity. The most frequently occurring Grade 3 and Grade 4 adverse events were: fatigue (30%), alanine aminotransferase increase (9%), confusional state (9%), lipase increase (9%), lymphopenia (9%), convulsion (7%), headache (7%), and hypophosphatemia (7%). Adverse events of special interest were: hypertension (all incidences, 39%; Grade 3/4, 7%), palmar-plantar erythrodysesthesia (30%; 7%), bleeding events (28%; 9%), proteinuria (26%; 0%), pulmonary embolism (9%; 7%) and craniotomy wound dehiscence (4%; 2%).

In the study, 87% of patients had a dose interruption of XL184, median average daily dose was 122 mg/day. XL184 will be evaluated at a lower dose of 125 mg daily in order to provide continuous and sustained exposure to the drug in this previously treated glioblastoma population.

Correlative tumor profiling and biomarker evaluation and vascular imaging data from this trial will also be presented in two additional posters in the same poster session. Abstract 2048, entitled “Neurovascular imaging in GBM patients quantifies early physiologic changes after treatment with XL184, an inhibitor of multiple receptor tyrosine kinases: results from a Phase 2 study” will be presented by Gregory Sorensen, MD, from the Massachusetts General Hospital, Boston, MA, and abstract 2049, entitled “Correlative tumor molecular profiling and plasma biomarker analysis in a phase 2 study of XL184 in patients with progressive or recurrent glioblastoma multiforme” will be presented by Samuel DePrimo, PhD, Exelixis Inc, South San Francisco, CA.

About XL184

XL184 (BMS-907351) is a small molecule designed to inhibit MET, VEGFR2, and RET. MET is a receptor tyrosine kinase that plays a key role in cellular proliferation, migration, and angiogenesis. These biological processes contribute to the transformation, progression, survival, and metastasis of cancer cells. MET is mutationally activated in some tumor types, such as hereditary and sporadic papillary renal cell carcinoma and some head and neck cancers. More frequently, MET is either over-expressed or activated in the absence of mutation in glioblastomas, breast carcinomas, some gastric cancers, and other solid tumors. MET amplification has been demonstrated in some NSCLCs. Expression of VEGF has been observed in a variety of cancers and has been associated with prognostic significance. Targeting the VEGF receptor has been recognized as a potential anti-cancer strategy in multiple tumors. Dual targeting of MET and VEGFR2 blocks two of the major mechanisms tumors use to overcome hypoxia. Activated RET is involved in cell signaling cascades that regulate cell proliferation, migration, differentiation, and survival. RET is mutationally activated in papillary thyroid cancer (PTC) and in both familial and sporadic forms of medullary thyroid cancer (MTC). Exelixis is co-developing XL184 with Bristol-Myers Squibb Company, and is currently conducting multiple clinical studies for XL184.

About Exelixis

Exelixis, Inc. is a development-stage biotechnology company dedicated to the discovery and development of novel small molecule therapeutics for the treatment of cancer and other serious diseases. The company is leveraging its fully integrated drug discovery platform to fuel the growth of its development pipeline, which is primarily focused on cancer. Currently, Exelixis’ broad product pipeline includes investigational compounds in phase 3, phase 2, and phase 1 clinical development. Exelixis has established strategic corporate alliances with major pharmaceutical and biotechnology companies, including Bristol-Myers Squibb, sanofi-aventis, GlaxoSmithKline , Genentech, Boehringer Ingelheim, Wyeth Pharmaceuticals, and Daiichi-Sankyo. For more information, please visit the company’s web site at http://www.exelixis.com.

Source
Bristol-Myers Squibb