With PCF support through every step of development, this new drug will soon make its way to castrate-resistant patients in record time.

November 7, 2011

Fast on the heels of five new prostate cancer drugs approved for patients with advanced disease in the past 18 months, a promising new drug, MDV3100 (Medivation and Astellas), should soon be approved by the FDA for patients who have failed hormone therapy and chemotherapy with docetaxel. The companies at the close of last week announced that, based on positive trial data, the Phase 3 AFFIRM Trial of MDV3100 will be stopped early and the drug will be offered to men in the placebo arm of the study.

The development of MDV3100 began with a PCF Board of Directors meeting at UCLA where the world’s top cancer scientists in leukemia were invited to apply for funding and work on prostate cancer. What then ensued was a competitive CaPCure (PCF) research award to Owen Witte, MD, Michael Jung, PhD, and Charles Sawyers, MD in 2002. The drug has a novel mechanism of action, inhibiting androgen receptor (AR) at three distinct points in the signaling pathway. In the study, MDV3100 increased median survival by 4.8 months, providing a 37% reduction in the risk of death compared to placebo. Some patients have very durable remissions well beyond the average and some do not respond so the median survival is a statistical description for the FDA and clinical researchers.
  
This is the second time the trial of a prostate cancer drug was stopped and the drug offered to patients in the placebo arm. The first such incidence was with abiratrone (Zytiga) which was approved earlier this year.

“The clinical advancement of MDV3100 is one of the most important events in the history of prostate cancer research and PCF,” says Howard Soule, chief scientist for PCF. “For men whose disease has progressed since receiving hormone and chemo therapies, MDV 3100 should provide a new treatment option to extend survival.”
MDV3100 directly blocks the activity of the androgen receptor, the engine of prostate cancer progression. Abiraterone affects prostate cancer progression by shutting off the supply of fuel, testosterone. Having both drugs available to patients will represent an important advance in patient treatment. Both drugs are being evaluated in Phase 3 trials in CRPC chemo naïve patients. Results are not yet available but the trend will be to use both medications earlier in the natural history of the disease. Both drugs are also being tested in the pre-surgical setting (funded by PCF Challenge Awards) with curative intent for primary high risk prostate cancer.

Many additional clinical trials are needed to determine the optimal sequence or combination of abiraterone and MDV3100 and to determine if combinations of MDV3100 with other experimental targeted therapies are synergistic.

Headed To Patients in Record Time

Equally impressive as the trials data for MDV3100 is the research and development period that has been a comparatively short nine years. PCF’s total investment of $14.75 million in MDV3100, supported by the PCF’s investment in the Prostate Cancer Clinical Trials Consortium, accelerated the drug’s progression. Medivation plans to meet with the U.S. Food and Drug Administration in early 2012 to discuss when they might seek approval for MDV3100.