SAN FRANCISCO, CA and TOKYO, JAPAN – September 10, 2014 – Medivation, Inc. (Nasdaq: MDVN) and Astellas Pharma Inc. (Tokyo: 4503) announced today that the U.S. Food and Drug Administration (FDA) approved a new indication for the use of XTANDI® (enzalutamide) capsules to treat patients with metastatic castration-resistant prostate cancer (CRPC). This new approved use follows a priority review of the supplemental New Drug Application (sNDA) that was based on results of the Phase 3 PREVAIL trial.

The FDA initially approved XTANDI, an oral, once-daily androgen receptor inhibitor, in August 2012 for use in patients with metastatic CRPC who previously received docetaxel (chemotherapy). The new indication approves XTANDI for use in men with metastatic CRPC who have not received chemotherapy. Metastatic CRPC is defined as a cancer that has spread beyond the prostate gland and has progressed despite treatment to lower testosterone (i.e., with a gonadotropin-releasing hormone (GnRH) therapy or with removal of the testes).  

“The FDA’s priority review and approval of this new indication for XTANDI now enables the use of an important therapy by patients with metastatic castration-resistant prostate cancer at all stages of their disease,” said Sef Kurstjens, M.D., Ph.D., chief medical officer of Astellas Pharma Inc. and president of Astellas Pharma Global Development, Inc.  “We are pleased that these patients now have XTANDI available as a treatment option.”

“All of us at Medivation extend our thanks to the clinicians and patients who participated in the PREVAIL clinical trial culminating in today’s approval,” said David Hung, M.D., founder, president and chief executive officer, Medivation, Inc. “As a company dedicated to the rapid development of novel therapies to treat serious diseases, we are pleased to see XTANDI approved in this important patient population.”

In the Phase 3 PREVAIL trial, men receiving XTANDI and GnRH therapy exhibited a statistically significant improvement in both overall survival and delayed time to radiographic progression or death as compared to those on placebo and GnRH therapy.   

XTANDI significantly reduced the risk of radiographic progression or death by 83% compared with placebo (HR=0.17; p < 0.0001).
XTANDI significantly reduced the risk of death by 29% compared with placebo (HR=0.71; p < 0.0001).   

When compared to placebo, treatment with XTANDI also delayed time to initiation of chemotherapy and time to a skeletal related event.

The safety profile for XTANDI was updated to reflect data from both the AFFIRM and PREVAIL Phase 3 trials.

Seizure occurred in 0.9% of patients receiving XTANDI who previously received docetaxel and 0.1% of patients who were chemotherapy-naive. 
The most common adverse reactions (≥ 10%) that occurred more commonly (≥ 2% over placebo) in the XTANDI-treated patients from the two randomized clinical trials were asthenia/fatigue, back pain, decreased appetite, constipation, arthralgia, diarrhea, hot flush, upper respiratory tract infection, peripheral edema, dyspnea, musculoskeletal pain, weight decreased, headache, hypertension, and dizziness/vertigo.

“Enzalutamide has been studied and is approved for patients with metastatic prostate cancer that is resistant to primary hormonal therapy, a disease state we call castration-resistant prostate cancer. In this setting, enzalutamide has been shown to extend overall survival and significantly delay the progression of prostate cancer,” said Tomasz M. Beer, M.D., F.A.C.P., co-principal investigator of the PREVAIL study, deputy director of the Knight Cancer Institute and professor of medicine at Oregon Health & Science University. “Furthermore, in the PREVAIL trial, the median time to initiating chemotherapy was delayed by 17 months with enzalutamide treatment as compared to placebo, so the result is a meaningful period of time during which men have their disease controlled without the need for chemotherapy.”

A variation application to amend the European Marketing Authorization Application based on the results of PREVAIL was validated for review by the European Medicines Agency on April 24, 2014.

The approval of this new indication for XTANDI triggers $90 million in milestone payments to Medivation under its collaboration agreement with Astellas.