The US Food and Drug Administration (FDA) approval for Xtandi (enzalutamide) capsules for the treatment of patients with metastatic castration-resistant prostate cancer who have previously received docetaxel. Xtandi is an oral, once-daily androgen receptor inhibitor.

The US FDA accepted the Xtandi New Drug Application (NDA) on July 23, 2012, and granted the filing Priority Review Designation with a Prescription Drug User Fee Act (PDUFA) action date of November 22, 2012. Medivation and Astellas expect to make Xtandi available to patients in the United States in mid-September 2012. Separately, a Marketing Authorization Application for Xtandi has been accepted for review by the European Medicines Agency (EMA).

“Today’s approval marks a significant accomplishment for Medivation. We are proud to be in a position to offer a new treatment, Xtandi, for this patient population for which there is a significant unmet medical need,” said David Hung, MD, co-founder, president and CEO, Medivation, Inc. “I would like to extend my thanks to the patients, physicians, and their study teams who participated in the clinical trials, and to our employees, and those of our partner Astellas, who have been instrumental in helping us reach this important milestone.”

“Enzalutamide provides an exciting new option for physicians that can prolong the lives of patients with metastatic prostate cancer who have received chemotherapy,” said Howard I Scher, MD, chief, Genitourinary Oncology Service, Sidney Kimmel Centre for Prostate and Urologic Cancers, Memorial Sloan-Kettering Cancer Centre, and the co-principal investigator of the AFFIRM pivotal study. “It is extremely gratifying to have led the clinical trial of enzalutamide, having followed the development of this drug from its early inception in the laboratory to the clinic.”

“We believe Xtandi has the potential to play an important role in the treatment of advanced prostate cancer,” said Stephen Eck, MD, PhD, vice president of Medical Oncology, Astellas Pharma Global Development. “We’re eager to work with Medivation to make this much-needed new treatment available to medical professionals and patients in September.”

The recommended dose of Xtandi is 160 mg (four 40 mg capsules) administered orally once daily. Xtandi can be taken with or without food and does not require concomitant steroid (e.g., prednisone) use. In the phase III clinical trial, 48 per cent of Xtandi patients and 46% of patients in the placebo arm were treated with glucocorticoids.

As a post-marketing requirement, Medivation and Astellas have agreed with the FDA to conduct an open-label safety study of Xtandi (160 mg/day) in patients who are at high risk for seizure. Medivation and Astellas have agreed to provide the data from this study in 2019.

Xtandi is an androgen receptor inhibitor indicated for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) who have previously received docetaxel. The efficacy and safety of Xtandi were assessed in a randomized, placebo-controlled, multi-centre phase III clinical trial. A total of 1,199 patients with mCRPC who had previously received docetaxel were randomized 2:1 to receive either Xtandi orally at a dose of 160 mg once daily (N = 800) or placebo (N = 399). Patients with a history of seizure, taking medications known to decrease the seizure threshold, or with other risk factors for seizure were excluded from the clinical trial. The primary endpoint of the trial was overall survival.

Xtandi-treated patients had a statistically-significant improvement in median overall survival compared to the placebo group: 18.4 months in the Xtandi group versus 13.6 months in the placebo group (P<0.0001). Xtandi provided a 37 per cent reduction in risk of death compared to placebo (hazard ratio = 0.631). Seizure occurred in 0.9 per cent of patients on Xtandi and 0 per cent of the placebo-treated patients.

The most common adverse reactions (= 5 per cent) are asthenia/fatigue, back pain, diarrhoea, arthralgia, hot flush, peripheral edema, musculoskeletal pain, headache, upper respiratory infection, muscular weakness, dizziness, insomnia, lower respiratory infection, spinal cord compression and cauda equina syndrome, hematuria, paresthesia, anxiety, and hypertension. Grade 3 and higher adverse reactions were reported among 47 per cent of Xtandi treated patients and 53 per cent of placebo-treated patients.

Xtandi (enzalutamide) is an androgen receptor inhibitor that acts on different steps in the androgen receptor signaling pathway. Xtandi has been shown to competitively inhibit androgen binding to androgen receptors and inhibit androgen receptor nuclear translocation and interaction with DNA. A major metabolite, N-desmethyl enzalutamide, exhibited similar in vitro activity to Xtandi. Xtandi decreased proliferation and induced cell death of prostate cancer cells in vitro, and decreased tumor volume in a mouse prostate cancer xenograft model.

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.

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