Oregon Health & Science University Cancer Institute is one of the first three centers in the world to offer a new drug, MDV3100, to participants in this prostate cancer research study. Tomasz Beer, M.D., the Grover C. Bagby Endowed Chair for Cancer Research, director of the Prostate Cancer Research Program at the OHSU Cancer Institute, contributed to the study's design and has involved significant role in this research.
The drug, developed by Medivation, Inc. showed encouraging anti-tumor activity in an advanced form of late-stage prostate cancer that usually does not respond to available therapies.
"Studies like this are emblematic of the core beliefs that define the OHSU Cancer Institute. It is only through the understanding of how cancer works, or what makes cancer tick, that we will find a way to vanquish cancer. Basic research told us that the androgen receptor is a key Achilles' heel of prostate cancer, even after initial hormonal therapy. This understanding resulted in the development of MDV3100. This is the creed that brought us Gleevec and drives all of us at the OHSU Cancer Institute," said Beer, associate professor of medicine (hematology/medical oncology), OHSU School of Medicine. Gleevec was the first targeted cancer pill and was developed at OHSU Cancer Institute. "We are proud of the fact that Oregonians were among the very first patients in the world to get access to this innovative drug."
Medivation, Inc. announced today that data from the ongoing clinical trial of the company's novel androgen receptor antagonist, MDV3100, showed encouraging anti-tumor activity as measured by declining serum levels of prostate specific antigen (PSA) and circulating tumor cells (CTC), as well as radiographic disease stabilization after three months of treatment. An increased number of androgen receptors present on prostate cancer cells is believed to play a major role in the growth of castration-resistant prostate cancer, also known as hormone-refractory prostate cancer. The observed clinical effects of MDV3100 on PSA levels, CTC counts and radiographic disease are consistent with blockade of androgen receptor signaling and inhibition of tumor growth. To date, 90 patients have been enrolled in the trial with enrollment completed at doses up to 240 mg/day. MDV3100 has been well-tolerated and dose escalation at 360 mg/day is in progress.
The data is being presented today at the American Society of Clinical Oncology 2008 Annual Meeting in Chicago in an oral presentation entitled "Phase 1-2 study of MDV3100 in patients (pts) with progressive Castration-Resistant Prostate Cancer (CRPC)" by principal investigator, Howard Scher, M.D., chief of the Genitourinary Oncology Service and the D. Wayne Calloway Chair in Urologic Oncology at Memorial Sloan-Kettering Cancer Center in New York.
The ongoing Phase 1-2 trial is an open-label U.S. dose-escalation study enrolling prostate cancer subjects who have failed standard hormonal therapies. The dose-expansion study has enrolled 84 study participants in three cohorts (60, 150, 240 mg/day) to date. Scher's presentation covered PSA data from all patients who have been followed for at least 12 weeks, the standard minimum duration of observation used to assess the treatment effects of prostate cancer drugs. Of the 42 chemo-naïve and 31 post-chemotherapy evaluable subjects across the three dose levels, 23 patients (55 percent) and 13 patients (42 percent) showed PSA declines greater than 50 percent at week 12 compared to baseline, respectively. Of the 28 evaluable subjects from the 240 mg/day dose group of the trial, 8 patients (29 percent) experienced a decline in PSA levels of greater than 90 percent compared to 9 percent and 13 percent in the 60 mg/day and 150 mg/day dose groups, respectively.
The number of CTC in a sample of a prostate cancer patient's blood can indicate prognosis; subjects with higher CTC counts (greater than or equal to five) are thought to have less favorable prognoses. MDV3100 treatment preserved favorable prognosis CTC counts below five in 92 percent of subjects in both dose groups and decreased the number of CTC counts to a favorable prognosis in 33 percent of subjects in the 60 mg/day dose group and in 56 percent of subjects in the 150 mg/day dose group.
Importantly, radiographic data in both the 60-mg and 150-mg dosing cohorts showed stabilization of disease through 12 weeks of treatment. Of the 15 evaluable subjects with soft tissue, 12 (80 percent) subjects had stabilization of disease. Prior to enrollment in this study, all these study participants had progressive disease despite standard of care hormonal therapies and in roughly half the subjects, also chemotherapy. As opposed to most previous studies in CRPC that have used the RECIST criteria to define evaluable patients and assess radiographic changes, these data were analyzed using the more recent and rigorous Prostate Cancer Clinical Trials Working Group (PCWG2) consensus guidelines.
"Castration-resistant prostate cancer is a devastating disease with high mortality rates and limited treatment options," said Scher. "MDV3100 has been well-tolerated and early results suggest encouraging anti-tumor activity. Additional data currently being generated will clarify its role as a potential therapy for patients with castration-resistant prostate cancer."
"We continue to be very encouraged by the results with MDV3100 obtained to date," said David Hung, M.D., president and chief executive officer of Medivation. "Analysis of the data showed a dose-dependent effect of MDV3100 on PSA levels, CTC counts and clinical outcomes. We continue to gather longer-term data on these subjects and are also exploring higher doses."
Medivation expects to complete the study, and report final top-line results, in 2008. If these results are positive, Medivation expects to seek U.S. Food and Drug Administration (FDA) agreement to enter a pivotal Phase 3 registration study in castration-resistant prostate cancer.
About Prostate Cancer
Prostate cancer is the most common non-skin cancer in the United States and the third most common cancer worldwide. More than 1 million men in the United States have prostate cancer. An estimated 186,320 new cases are expected to be diagnosed in 2008, and approximately 28,660 men are expected to die this year from the disease. Patients with castration-resistant (also known as hormone-refractory) prostate cancer have few treatment options and a poor prognosis.
About the OHSU Cancer Institute
The OHSU Cancer Institute is the only National Cancer Institute-designated center between Sacramento and Seattle. It comprises some 200 clinical researchers, basic scientists and population scientists who work together to translate scientific discoveries into longer and better lives for Oregon's cancer patients. In the lab, basic scientists examine cancer cells and normal cells to uncover molecular abnormalities that cause the disease. This basic science informs more than 300 clinical trials conducted at the OHSU Cancer Institute.
Medivation, Inc. is a biopharmaceutical company focused on the rapid development of novel small molecule drugs to treat serious diseases of the central nervous system and cancers for which there are limited treatment options. Medivation aims to revolutionize the treatment of these diseases and offer hope to critically ill patients and their caregivers. The Company's current clinical development program includes a pivotal and confirmatory Phase 3 trial of DimebonTM in Alzheimer's disease, a Phase 2 clinical trial of Dimebon in patients with Huntington's disease, and a Phase 1-2 clinical trial of MDV3100 in patients with castration-resistant (also known as hormone-refractory) prostate cancer. For more information, please visit us at www.medivation.com.
This press release contains forward-looking statements, including statements regarding anticipated clinical and regulatory milestones, which are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements involve risks and uncertainties that could cause actual results to differ significantly from those projected. You are cautioned not to place undue reliance on the forward-looking statements, which speak only as of the date of this release. None of the Company's product candidates has been approved for sale, significant additional animal and human testing is required in order to seek marketing approval for any of its product candidates, and Medivation cannot assure you that marketing approval can beobtained for any of its product candidates. Furthermore, as is typically the case at this stage of the regulatory review process, the FDA has not yet performed an in-depth review of Medivation's preclinical and clinical data, so its views remain subject to change. Medivation's filings with the Securities and Exchange Commission, including its Annual Report on Form 10-KSB for the year ended December 31, 2007 and its Quarterly Report on Form 10-Q for the quarter ended March 31, 2008, include information about additional factors that could affect the Company's financial and operating results.