San Francisco, CA and Tokyo – October 22, 2013 – Medivation, Inc. (Nasdaq: MDVN) and Astellas Pharma Inc. (TSE: 4503) today announced that the Independent Data Monitoring Committee (IDMC) has informed the companies of positive results from a planned interim analysis of the global Phase 3 PREVAIL trial of enzalutamide in more than 1,700 men with metastatic prostate cancer that has progressed despite androgen deprivation therapy and who have not yet received chemotherapy. Given the observed benefits in the trial’s co-primary endpoints of overall survival and radiographic progression-free survival, and considering the observed safety profile, the IDMC concluded enzalutamide demonstrated a favorable benefit-risk ratio. The IDMC recommended the study be stopped and patients treated with placebo be offered enzalutamide. Additional data from the Phase 3 PREVAIL results, including safety data, will be submitted for presentation at an upcoming medical conference.
The IDMC informed the companies of the following results:
Patients treated with enzalutamide demonstrated a statistically significant overall survival advantage compared with patients receiving placebo (p<0.0001). Enzalutamide provided a 30% reduction in risk of death compared with placebo (Hazard Ratio=0.70; 95% confidence interval, 0.59-0.83).
Patients treated with enzalutamide demonstrated a statistically significant radiographic progression-free survival advantage compared with patients receiving placebo (p<0.0001). Enzalutamide provided an 81% reduction in risk of radiographic progression or death compared with placebo (Hazard Ratio=0.19; 95% confidence interval, 0.15-0.23).
The percentage of patients alive in the enzalutamide arm was 72% as compared with 65% in the placebo arm at the time of the interim analysis data cut-off date. Treatment with enzalutamide resulted in a calculated point estimate for median overall survival of 32.4 months (95% confidence interval, 31.5 months-upper limit not yet reached) versus 30.2 months (95% confidence interval, 28.0 months-upper limit not yet reached) for patients receiving placebo. Because the trial will be stopped early with the majority of patients still alive, the estimated median survivals are not as precise as the hazard ratio. The hazard ratio takes into account available information about the trial endpoint from all patients whereas the median is a single point estimate of a much smaller number of patients at risk.
The median radiographic progression-free survival was not yet reached (95% confidence interval, 13.8 months-upper limit not yet reached) in the enzalutamide arm and was 3.9 months (95% confidence interval, 3.7-5.4) in the placebo arm.
Given the overall survival benefit and the observed safety profile, the IDMC considered the overall benefit-risk ratio to favor the enzalutamide arm and recommended unequivocally that patients receiving placebo be offered treatment with enzalutamide.
Of the 1,715 patients treated in the blinded PREVAIL study, two patients were reported by investigators to have had a seizure event. The full analysis of the safety data will become available upon final database lock and unblinding.
“To my knowledge, the benefits in overall survival and radiographic progression-free survival reported in today's PREVAIL trial results are unprecedented in this patient population,” said Tomasz M. Beer, M.D., F.A.C.P., professor of medicine and deputy director of the Knight Cancer Institute at Oregon Health & Science University, and the co-principal investigator of the PREVAIL study.
“Achieving statistically-significant and clinically meaningful results in both co-primary endpoints ̶ overall survival and radiographic progression-free survival ̶ is an important outcome for patients and we are excited by the results of the Phase 3 PREVAIL trial,” said David Hung, M.D., founder, president and CEO, Medivation. “I extend my sincere thanks to the patients, physicians, study teams and other collaborators around the world, who have been instrumental in helping us achieve this important milestone.”
"We are very pleased about these results and will work closely with Medivation to pursue an expanded indication for enzalutamide," said Sef Kurstjens, M.D., Ph.D., Chief Medical Officer of Astellas. "We are committed to being at the forefront of the fight against prostate cancer by providing patients with treatment options to help them manage their disease.”
Medivation and Astellas will initiate meetings with and submissions to regulatory agencies beginning in early 2014.
The Phase 3 PREVAIL trial is a randomized, double-blind, placebo-controlled, multi-national trial that enrolled more than 1,700 patients at sites in the United States, Canada, Europe, Australia, Russia, Israel and Asian countries including Japan. The trial enrolled patients with metastatic prostate cancer whose disease progressed despite treatment with androgen deprivation therapy and had not yet received chemotherapy. The co-primary endpoints of the trial are overall survival and radiographic progression-free survival. The trial was designed to evaluate enzalutamide at a dose of 160 mg taken orally once daily versus placebo. Targeted enrollment was completed in May 2012 and the interim analysis was pre-specified after 516 events (patient deaths).