CHERTSEY, England--(BUSINESS WIRE)--Astellas Pharma Europe Ltd. today announced that the European Commission (EC) has granted a variation to amend the Marketing Authorisation for enzalutamide (trade name XTANDI™).1 Enzalutamide is now approved in Europe for the treatment of adult men with metastatic castration-resistant prostate cancer (mCRPC) who are asymptomatic or mildly symptomatic after failure of androgen deprivation therapy in whom chemotherapy is not yet clinically indicated.1
The Marketing Authorisation approval is based on results from the pivotal phase III PREVAIL study which demonstrate that enzalutamide improves outcomes for men with advanced prostate cancer who have not received chemotherapy.2"Enzalutamide provides a viable treatment option for a broad population of men with mCRPC, regardless of age, or their readiness for chemotherapy, which provides a meaningful period of time during which men have their disease controlled without the need for chemotherapy", said Professor Bertrand Tombal, MD, PhD, Chairman of the Division of Urology and Professor of Physiology, Université Catholique de Louvain (UCL) and European Principal Investigator for PREVAIL. "The decision from the European Commission to approve enzalutamide, an effective and well tolerated alternative to chemotherapy, is a very important milestone for men with prostate cancer that has advanced."
Compared with placebo, enzalutamide reduced the risk of death by 29% (HR=0.71; p<0.001) and the risk of radiographic progression or death by 81% (HR=0.19; p<0.001). Men treated with enzalutamide experienced a 17-month delay in the time to initiation of chemotherapy compared to placebo (28.0 months versus 10.8 months, respectively; HR=0.35; p<0.001).2
The most common clinically relevant adverse events among the enzalutamide population as compared with placebo-treated patients in the PREVAIL trial included fatigue, hot flush and hypertension. Hypertension was observed in 13% of enzalutamide versus 4% of placebo-treated patients. Grade 3 or higher cardiac adverse events were reported in 3% of enzalutamide versus 2% of placebo-treated patients. One patient (0.1%) out of the 871 patients treated with enzalutamide, and one patient (0.1%) out of 844 patients receiving placebo experienced a seizure.2
Enzalutamide was approved by the EC in June 2013 for the treatment of adult men with mCRPC whose disease has progressed on or after docetaxel therapy.3 The new indication makes enzalutamide available for men in whom chemotherapy is not yet clinically indicated. Astellas expects to launch enzalutamide in the chemotherapy-naïve setting in the first European countries, including the UK, from December 2014.
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Notes to editors
About the PREVAIL Trial
The Phase III PREVAIL trial is a randomised, 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 Asia including Japan. The trial enrolled patients with chemotherapy-naïve metastatic prostate cancer whose disease progressed on a luteinising hormone-releasing hormone analogue or after bilateral orchiectomy. 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.2
About XTANDI™ (enzalutamide)
Enzalutamide is a novel, oral, once-daily androgen receptor signalling inhibitor. Enzalutamide directly targets the androgen receptors (AR) and exerts its effects on all three steps of AR signalling pathway:
Blocks androgen binding4
- Androgen binding induces a conformational change that triggers activation of the receptor5
Prevents nuclear translocation4
- Transit of the AR to the nucleus is an essential step in AR-mediated gene regulation5
Impairs DNA binding4
- Binding of the AR to the DNA is essential for modulation of gene expression5
Enzalutamide was first approved by the European Commission in June 2013 for the treatment of adult men with mCRPC whose disease has progressed on or after docetaxel therapy.3 Enzalutamide is now approved in Europe for the treatment of adult men with metastatic castration-resistant prostate cancer who are asymptomatic or mildly symptomatic after failure of androgen deprivation therapy in whom chemotherapy is not yet clinically indicated.1
Important Safety Information for XTANDI™ (enzalutamide)
For important Safety Information for enzalutamide please see the full Summary of Product Characteristics at:http://www.medicines.org.uk/emc/medicine/27912/SPC/Xtandi+40mg+soft+capsules/.
Astellas Pharma Europe Ltd. operates in 40 countries across Europe, the Middle East and Africa, and is the regional business of Tokyo-based Astellas Pharma Inc. Astellas is a pharmaceutical company dedicated to improving the health of people around the world through the provision of innovative and reliable pharmaceuticals. The organisation's focus is to deliver outstanding R&D and marketing to continue growing in the world pharmaceutical market. Astellas' presence in Europe also includes an R&D site and three manufacturing plants. The company employs approximately 4,350 staff across these countries. For more information about Astellas Pharma Europe Ltd., please visit www.astellas.eu.
About the Astellas/Medivation Collaboration
In October 2009, Medivation Inc. (Nasdaq: MDVN) and Astellas entered into a global agreement to jointly develop and commercialise 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 commercialise enzalutamide in the United States and Astellas has responsibility for manufacturing and all additional regulatory filings globally, as well as commercialising enzalutamide outside the United States.
1 European Medicines Agency – XTANDI (enzalutamide)
2 Beer TM, et al. Enzalutamide in Metastatic Prostate Cancer before Chemotherapy. N Engl J Med 2014; DOI: 10.1056/NEJMoa1405095
3 European Medicines Agency. XTANDI (enzalutamide). Summary of Product Characteristics, 2013
4 Tran C, et al. Development of a second-generation antiandrogen for treatment of advanced prostate cancer. Science 2009; 324:787-790
5 Hu R, Denmeade SR and Luo J. Molecular processes leading to aberrant androgen receptor signaling and castration resistance in prostate cancer. Expert Rev Endocrinol Metab 2010; 5 (5): 753–764