SAN FRANCISCO, CA AND TOKYO, JAPAN – January 28, 2014 – Medivation Inc. (NASDAQ: MDVN) and Astellas Pharma Inc. (TSE: 4503) announced final results on the primary and secondary efficacy endpoints from the Phase 3 PREVAIL trial of enzalutamide in patients with chemotherapy-naïve metastatic prostate cancer who have failed androgen deprivation therapy and have few or no symptoms. Data will be shared in a late-breaking oral presentation at the upcoming American Society of Clinical Oncology (ASCO) 2014 Genitourinary (GU) Cancers Symposium in San Francisco on Thursday, January 30, 2014.
“The PREVAIL study results demonstrate for the first time a statistically significant reduction both in the risk of death and a delay in cancer progression in men with metastatic prostate cancer who have a rising PSA and few, if any, symptoms," 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 co-principal investigator of the PREVAIL study. "The scope of the efficacy endpoints and the safety profile in PREVAIL, including the length of time that chemotherapy can be delayed, would represent a step forward for men with prostate cancer.”
The PREVAIL study results in men with metastatic prostate cancer who have progressed on androgen deprivation therapy are as follows:
Treatment with enzalutamide demonstrated a statistically significant overall survival benefit compared with placebo treatment. Enzalutamide reduced the risk of death by 29% (HR=0.71; p<0.0001), compared with placebo. This benefit was observed despite substantial use of subsequent therapies (40% in the enzalutamide and 70% in the placebo groups).
Treatment with enzalutamide significantly reduced the risk of radiographic progression or death by 81% compared with placebo treatment (HR=0.19; p<0.0001).
Consistent benefits on these co-primary endpoints of overall survival and radiographic progression-free survival were observed across patient subgroups.
Men taking enzalutamide experienced a 17-month delay in the time to initiation of chemotherapy compared with men taking placebo (28.0 months versus 10.8 months; HR=0.35; p<0.0001).
The majority of men (58.8%) with soft tissue metastatic disease treated with enzalutamide versus 5% of patients treated with placebo had objective responses (complete responses or partial responses) including complete responses in 19.7% of enzalutamide patients compared with 1% of placebo patients.
Enzalutamide extended the median time to PSA progression from 2.8 months (placebo) to 11.2 months (HR= 0.169; p < 0.0001).
Nearly 4 out of 5 patients in the enzalutamide group experienced a PSA decline of 50% or more, compared to less than 4% in the placebo group (78% vs. 3.5%; p<0.0001).
The median times to deterioration in a measure of prostate cancer-specific quality of life, the Functional Assessment of Cancer Therapy-Prostate or FACT-P, were 11.3 months for the enzalutamide-treated patients and 5.6 months for the placebo patients (HR=0.625, p < 0.0001).
The median treatment duration for enzalutamide was more than 3 times longer than for placebo (16.6 versus 4.6 months).
Common side effects occurring during treatment and more common in the enzalutamide treated men included fatigue, back pain, constipation and arthralgia. Hypertension was observed in 13.4% of enzalutamide versus 4.1% of placebo-treated patients. Grade 3 or higher cardiac adverse events were reported in 2.8% of enzalutamide versus 2.1% of placebo-treated patients. Investigators reported zero seizures in the enzalutamide-treated group and one in the placebo group prior to the data cutoff date. One seizure was reported in the enzalutamide group after the data cutoff date.
“Medivation's primary mission is to develop and make available to patients medically innovative therapies that provide clinically meaningful benefits and address major medical unmet needs among a spectrum of serious diseases,” said David Hung, M.D., founder, president and CEO of Medivation. “Should enzalutamide be approved for use in this patient population, it will be a meaningful advance in the field of prostate cancer therapy.”
“The PREVAIL study results are encouraging and we plan to submit, along with our partner Medivation, our regulatory applications to the U.S. Food and Drug Administration and European Medicines Agency in early 2014,” said Sef Kurstjens, M.D., Ph.D., and Chief Medical Officer of Astellas. "Astellas is committed to being a global category leader in the fight against cancer by providing patients with treatment options, such as enzalutamide, to manage their disease.”
Details of the presentation are as follows:
Title: Enzalutamide in men with chemotherapy-naïve metastatic prostate cancer (mCRPC): Results of Phase 3 PREVAIL Study
Presenter: Tomasz M. Beer, M.D., F.A.C.P., Knight Cancer Institute, Oregon Health & Science University
Session Detail: Welcome and General Session 1: Integrating Androgen Axis Therapy across the Disease Spectrum
Session Date/Time: January 30, 2014 from 7:45 a.m - 9:45 a.m.
About the PREVAIL Trial
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 were 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 pre-specified interim analysis was conducted after 516 events (patient deaths).