Astellas Pharma Europe Ltd., the European Headquarters of Tokyo-based Astellas Pharma Inc., and Medivation, Inc. have received a positive opinion from the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP), recommending European Commission (EC) approval for Xtandi (enzalutamide) capsules for the treatment of adult men with metastatic castration-resistant prostate cancer whose disease has progressed on or after docetaxel therapy.

Enzalutamide is a novel, once-daily, oral androgen receptor signalling inhibitor. It inhibits multiple steps in the androgen receptor (AR) signalling pathway, which has been shown to decrease cancer cell growth and can induce cancer cell death (apoptosis).

The positive CHMP opinion is based on results from the phase III AFFIRM study which confirmed that enzalutamide demonstrated a statistically significant improvement (p<0.0001) in overall survival compared to placebo, with a median survival of 18.4 months in the enzalutamide group versus 13.6 months in the placebo group, an advantage of 4.8 months [hazard ratio (HR) = 0.631]. The study also concluded that enzalutamide was generally well tolerated by patients and met all secondary endpoints.

The CHMP's positive recommendation will be reviewed by the European Commission (EC), which has authority to approve medicines for the European Union. Astellas anticipates a final decision from the EC shortly, as this usually occurs approximately 60 days after a CHMP recommendation.

Professor Johann de Bono, Professor of Experimental Cancer Medicine at The Institute of Cancer Research, London, and Head of the Drug Development Unit at The Royal Marsden NHS Foundation Trust, comments: “This is an important development in prostate cancer therapeutics that will provide a critically important new treatment option for patients with Combined medical and consumer health release advanced prostate cancer. Enzalutamide has a major impact on quality of life and survival from this common disease, and will hopefully become a key component of prostate cancer treatment initially in late stage disease following chemotherapy.”

Prostate cancer is the most frequently diagnosed cancer among European men and it is becoming more common. Advanced prostate cancer is defined as cancer that has spread outside of the prostate to other areas of the body (metastasised).

Patients with metastatic CRPC currently have few treatment options. There is an unmet need in this area for new compounds that target the cancer differently and which may provide alternative therapeutic options for patients at this late stage of their disease.

Enzalutamide is a novel, oral, once-daily androgen receptor signalling inhibitor. Enzalutamide inhibits androgen receptor signalling in three distinct ways: it inhibits testosterone binding to androgen receptors; nuclear translocation of androgen receptors; and DNA binding and activation by androgen receptors.

Xtandi (enzalutamide) was approved by the US Food and Drug Administration on August 31, 2012 for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) who have previously received docetaxel (chemotherapy).

The phase III AFFIRM trial is a randomised, double-blind, placebo-controlled, multinational trial evaluating enzalutamide (160 mg/day) versus placebo in 1,199 men with progressive metastatic castration-resistant prostate cancer who were previously treated with docetaxelbased chemotherapy. Enrolment was completed in November 2010 and the interim analysis was triggered at 520 events. The median age of study participants was 69 years at baseline. The AFFIRM study was conducted at sites in the United States, Canada, Europe, Australia, South America and South Africa.

The primary endpoint of the AFFIRM trial was overall survival. Key secondary endpoints included time to prostate-specific antigen (PSA) progression, radiographic progression free survival (rPFS) and time to first skeletal-related event (SRE).

Astellas Pharma Europe Ltd., is a pharmaceutical company dedicated to improving the health of people around the world through the provision of innovative and reliable pharmaceuticals.

Medivation, Inc. is a biopharmaceutical company focused on the rapid development of novel therapies to treat serious diseases for which there are limited treatment options.