SAN FRANCISCO, CA and TOKYO, JAPAN – December 10, 2014 – Medivation, Inc. (NASDAQ: MDVN) and Astellas Pharma Inc. (TSE: 4503) today announced that PREVAIL, the global Phase 3 trial of enzalutamide in metastatic castration-resistant prostate cancer (CRPC), was named the Clinical Advance of the Year by SCRIP, a leading pharmaceutical industry publication.
XTANDI® (enzalutamide) capsules is approved in the United States and Europe for the treatment of patients with metastatic CRPC and in Japan for the treatment of patients with CRPC. The companies are also conducting investigational studies of enzalutamide in prostate cancer and advanced breast cancer.
“The PREVAIL trial results have supported successful applications to extend the label of XTANDI to metastatic CRPC patients who are chemotherapy-naïve, marking a significant step forward in the treatment of this common cancer,” SCRIP noted.
The annual SCRIP Awards acknowledge the biopharmaceutical industry’s most noteworthy achievements and milestones. This year’s winners were announced at the SCRIP 10th Anniversary Awards celebration in London.
About PREVAIL
The Phase 3 PREVAIL trial was a randomized, double-blind, placebo-controlled, multi-national trial that enrolled more than 1,700 patients at sites around the world. The trial enrolled patients with metastatic prostate cancer whose disease progressed despite treatment with androgen deprivation therapy and had not yet received chemotherapy. The trial was designed to evaluate enzalutamide at a dose of 160 mg taken orally once daily versus placebo plus gonadotropin-releasing hormone (GnRH) therapy or after bilateral orchiectomy. Targeted enrollment was completed in May 2012 and the interim analysis was pre-specified after 516 events (patient deaths).
In October 2013, the Independent Data Monitoring Committee (IDMC) reported positive results from the interim analysis of the PREVAIL trial and determined that given the overall survival benefit and the observed safety profile, the overall benefit-risk ratio favored the enzalutamide arm. The IDMC recommended unequivocally that patients receiving placebo be offered treatment with enzalutamide. Therefore, the PREVAIL trial was halted and patients receiving placebo were offered enzalutamide. The trial met both co-primary endpoints of overall survival and radiographic progression-free survival.
About XTANDI® (enzalutamide) capsules
XTANDI is approved by the U.S. Food and Drug Administration and the European Medicines Agency for the treatment of patients with metastatic castration-resistant prostate cancer (CRPC). It is also approved in Japan for the treatment of patients with castration-resistant prostate cancer (CRPC).
Important Safety Information
Contraindications: XTANDI (enzalutamide) capsules can cause fetal harm when administered to a pregnant woman based on its mechanism of action and findings in animals. XTANDI is not indicated for use in women. XTANDI is contraindicated in women who are or may become pregnant.
Warnings and Precautions: In Study 1, conducted in patients with metastatic castration-resistant prostate cancer (CRPC) who previously received docetaxel, seizure occurred in 0.9% of patients who were treated with XTANDI and 0% treated with placebo. In Study 2, conducted in patients with chemotherapy-naïve metastatic CRPC, seizure occurred in 0.1% of patients who were treated with XTANDI and 0.1% treated with placebo. Patients experiencing a seizure were permanently discontinued from therapy and all seizure events resolved. There is no clinical trial experience re‐administering XTANDI to patients who experienced a seizure, and limited clinical trial experience in patients with predisposing factors for seizure. Study 1 excluded the use of concomitant medications that may lower threshold, whereas Study 2 permitted the use of these medications. Because of the risk of seizure associated with XTANDI use, patients should be advised of the risk of engaging in any activity during which sudden loss of consciousness could cause serious harm to themselves or others. Permanently discontinue XTANDI in patients who develop a seizure during treatment.
Adverse Reactions: The most common adverse reactions (≥ 10%) reported from the two combined clinical trials that occurred more commonly (≥ 2% over placebo) in the XTANDI-treated patients 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.
Other Adverse Reactions include:
• Laboratory Abnormalities: In the two studies, Grade 1‐4 neutropenia occurred in 15% of patients treated with XTANDI (1% Grade 3-4) and in 6% of patients treated with placebo (0.5% Grade 3-4). The incidence of Grade 1‐4 thrombocytopenia was 6% of patients treated with XTANDI (0.3% Grade 3-4) and 5% of patients on placebo (0.5% Grade 3-4). Grade 1-4 elevations in ALT occurred in 10% of patients treated with XTANDI (0.2% Grade 3-4) and 16% of patients treated with placebo (0.2% Grade 3-4). Grade 1-4 elevations in bilirubin occurred in 3% of patients treated with XTANDI (0.1% Grade 3-4) and 2% of patients treated with placebo (no Grade 3-4).
• Infections: In Study 1, 1% of XTANDI versus 0.3% of placebo patients and in Study 2, 1 patient in each treatment group (0.1%) had an infection resulting in death.
• Falls: In the two studies, falls including fall‐related injuries occurred in 9% of XTANDI patients vs 4% treated with placebo. Falls were not associated with loss of consciousness or seizure. Fall‐related injuries were more severe in XTANDI patients and included non‐pathologic fractures, joint injuries, and hematomas.
• Hypertension: In the two studies, hypertension was reported in 11% of patients receiving XTANDI and 4% of patients receiving placebo. No patients experienced hypertensive crisis. Medical history of hypertension was balanced between arms. Hypertension led to study discontinuation in < 1% of XTANDI or placebo treated patients.
Drug Interactions:
• Effect of Other Drugs on XTANDI ‐ Administration of strong CYP2C8 inhibitors can increase the plasma exposure to XTANDI. Co‐administration of XTANDI with strong CYP2C8 inhibitors should be avoided if possible. If co‐administration of XTANDI cannot be avoided, reduce the dose of XTANDI. Co‐administration of XTANDI with strong or moderate CYP3A4 and CYP2C8 inducers may alter the plasma exposure of XTANDI and should be avoided if possible.
• Effect of XTANDI on Other Drugs ‐XTANDI is a strong CYP3A4 inducer and a moderate CYP2C9 and CYP2C19 inducer in humans. Avoid CYP3A4, CYP2C9 and CYP2C19 substrates with a narrow therapeutic index, as XTANDI may decrease the plasma exposures of these drugs. If XTANDI is co‐administered with warfarin (CYP2C9 substrate), conduct additional INR monitoring.
For Full Prescribing Information for XTANDI (enzalutamide) capsules, please visit www.XtandiHCP.com/PI
About the Medivation/Astellas Collaboration
In October 2009, Medivation and Astellas entered into a global agreement to jointly develop and commercialize enzalutamide. The companies are collaborating on a comprehensive development program that includes studies to develop enzalutamide across the full spectrum of advanced prostate cancer as well as advanced breast cancer. The companies jointly commercialize XTANDI in the United States and Astellas has responsibility for manufacturing and all additional regulatory filings globally, as well as commercializing XTANDI outside the United States.
About Medivation Inc.
Medivation, Inc. is a biopharmaceutical company focused on the rapid development of medically-innovative therapies to treat serious diseases for which there are limited treatment options. Medivation aims to transform the treatment of these diseases and offer hope to critically ill patients and their families. For more information, visit www.medivation.com
About Astellas Pharma Inc.
Astellas Pharma Inc. is a pharmaceutical company dedicated to improving the health of people around the world through provision of innovative and reliable pharmaceuticals. The organization is committed to being a global category leader in Oncology and Urology, and has several oncology compounds in development in addition to enzalutamide. For more information on Astellas Pharma Inc., please visit our website at www.astellas.com/en.
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