It was announced yesterday that the Independent Data Monitoring Committee (IDMC) has informed the the pharmaceuticals, Medivation and Astellas of positive results from a planned interim analysis of the Phase 3 AFFIRM trial of MDV3100 in men with advanced prostate cancer previously treated with chemotherapy.

The monitoring committee found that MDV3100, the first androgen receptor signaling inhibitor, successfully met the study’s pre-specified interim efficacy stopping criteria, demonstrating a clinically meaningful and statistically significant (p < 0.0001) improvement in overall survival compared to placebo. As a result, the IDMC recommended that AFFIRM be stopped early and men who received placebo be offered MDV3100.

The results from the interim analysis showed that MDV3100 produced a 4.8-month advantace in median overall survival compared to placebo. The estimated median survival for men treated with MDV3100 was 18.4 months compared with 13.6 months for men treated with placebo.

MDV3100 provided a 37 percent reduction in risk of death compared to placebo (Hazard Ratio=0.631). The IDMC further determined, considering the observed safety profile, that MDV3100 demonstrated a favorable risk-to-benefit ratio sufficient to stop the study. A full analysis of the results from AFFIRM, including safety data, will be submitted for presentation at an upcoming scientific congress.
Howard I. Scher, M.D., chief, Genitourinary Oncology Service at Memorial-Sloan Kettering Cancer Center, and the co-principal investigator of the AFFIRM study said that “MDV3100 was rationally designed to target androgen receptor signaling, a key driver of prostate cancer growth, and the overall survival benefit the compound demonstrated in the AFFIRM interim analysis is significant….. If approved, MDV3100 will be a welcome option for men with prostate cancers that have progressed on hormones and initial chemotherapy.”

The mechanism of action used by “MDV3100 to inhibit androgen receptor signaling is at three distinct points in the signaling pathway,” said Professor Johann de Bono, M.D., MSc, Ph.D., FRCP, Honorary Consultant in Medical Oncology, Professor of Experimental Cancer Medicine, The Institute of Cancer Research and The Royal Marsden Hospital, and the co-principal investigator of the AFFIRM study. “I am thus particularly pleased with the results of the AFFIRM interim analysis, as there is a real need for new treatments in advanced prostate cancer that target the cancer in different ways.”

The Phase 3 AFFIRM trial is a randomized, double-blind, placebo-controlled, multinational trial evaluating MDV3100 (160 mg/day) versus placebo in 1,199 men with advanced prostate cancer who were previously treated with docetaxel-based chemotherapy. Enrollment was completed in November 2010 and the interim analysis was triggered at 520 events.

Medivation and Astellas plan to hold a pre-NDA meeting with the U.S. Food and Drug Administration (FDA) in early 2012 and will provide an update on regulatory timelines for MDV3100 subsequent to that meeting.

“These results are both an important step toward making this life-extending potential treatment available to the prostate cancer community and a significant milestone for our company,” said David Hung, M.D., president and CEO, Medivation. “Because we continue to believe that MDV3100 may also benefit patients with earlier-stage disease, we plan to continue studying the compound in a broad array of earlier prostate cancer disease settings while we pursue initial regulatory approval in post-chemotherapy patients. We extend sincere thanks to all the patients, investigators and employees who helped make this possible.”

MDV3100 MDV3100 is an oral, once a day investigational agent inhibits androgen receptor signaling in three distinct ways: it inhibits 1) testosterone binding to androgen receptors; 2) nuclear translocation of androgen receptors; and 3) DNA binding and activation by androgen receptors.

In addition to the AFFIRM trial in men with advanced prostate cancer previously treated with chemotherapy, MDV3100 is also being studied in the Phase 3 PREVAIL trial in 1,700 men with advanced prostate cancer who have not received chemotherapy, the Phase 2 TERRAIN trial in nearly 400 men whose disease has progressed while on luteinizing hormone releasing hormone (LHRH) analogue or hormone therapy, and a Phase 2 study in hormone-naive men.

Needless to say, this is some more great news for those of us dealing with advanced prostate cancer. Hopefully, we will be looking to the end of 2012 or beginning of 2013 for approvals.

Joel T. Nowak, M.A., M.S.W.