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Medivation, Inc. (MDVN) Says Astellas Pharma Inc. (YPH.BE) Submits MAA to European Medicines Agency for Enzalutamide

6/27/2012 6:30:25 AM

TOKYO, Jun 26, 2012 (BUSINESS WIRE) -- Today, Astellas Pharma Inc. (tokyo:4503)(tokyo:"Astellas"). announces the submission of a European marketing authorisation application to the European Medicines Agency (EMA) for enzalutamide (USAN*, MDV3100) for the treatment of men with metastatic castration-resistant prostate cancer who have been previously treated with docetaxel-based chemotherapy.

Enzalutamide is a novel, once-daily investigational oral androgen receptor signalling inhibitor and the submission follows positive results from the pivotal phase III AFFIRM study, which confirmed that enzalutamide demonstrated a statistically significant improvement (p<0.0001) in overall survival with a median improvement over placebo of 4.8 months [hazard ratio (HR) = 0.631](1). The study also concluded that enzalutamide was generally well tolerated by patients and met all secondary endpoints(1). A New Drug Application (NDA) has been submitted in the United States, where priority review of the compound has been requested(2).

"Data from clinical studies, including the phase III AFFIRM study, have demonstrated that enzalutamide significantly improves overall survival whilst providing a favourable tolerability profile for patients," said Professor Johann de Bono, M.D., MSc, Ph.D., FRCP, Honorary Consultant in Medical Oncology, Professor in Experimental Cancer Medicine, The Institute of Cancer Research, The Royal Marsden Hospital and co-principal investigator of the AFFIRM study. "This is vital for patients at this late stage of their disease and the submission of enzalutamide represents an important step towards making this promising treatment available to men with advanced prostate cancer across Europe."

In the phase III AFFIRM trial, common side effects observed more frequently in enzalutamide as compared with placebo-treated patients included fatigue, diarrhoea and hot flush. Seizure was reported in < 1% of enzalutamide-treated patients. Serious adverse events, adverse events causing patients to stop treatment, and adverse events causing death were all lower in the enzalutamide group than in the placebo group(1).

Further positive results from the AFFIRM study relating to the secondary endpoints of health-related quality of life and time to first skeletal-related events will also be presented this week at the Global Congress on Prostate Cancer, Brussels, Belgium(3). These data form one of four winning abstracts at the congress and will be presented by Professor Cora Sternberg of the Department of Medical Oncology, San Camillo Forlanini Hospital, Rome, Italy.

"Extending life for patients with advanced prostate cancer is of course a primary goal of treatment, but equally important is that we minimise the impact of treatment on patient quality of life", said Professor Sternberg.

To arrange an interview with Professor Johann de Bono, Professor Cora Sternberg or Dr Ian Banks from the European Men's Health Forum please contact Sarah Mckinnon Clark (details below).

* United States Adopted Name (USAN)

About Enzalutamide -- USAN (MDV3100)

Enzalutamide is a novel, oral, once-daily investigational agent that is an androgen receptor signalling inhibitor(1,4).Enzalutamide is not approved for use in Europe.

Enzalutamide inhibits androgen receptor signalling in three distinct ways: it inhibits 1) testosterone binding to androgen receptors; 2) nuclear translocation of androgen receptors; and 3) DNA binding and activation by androgen receptors(1,4).


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 metastatic castration-resistant prostate cancer who were previously treated with docetaxel-based 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(1).

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)(1).

In the phase III AFFIRM trial, enzalutamide was generally well tolerated. Common side effects observed more frequently in enzalutamide as compared with placebo-treated patients included fatigue, diarrhoea and hot flush. Seizure was reported in < 1% of enzalutamide-treated patients. Serious adverse events, adverse events causing patients to stop treatment, and adverse events causing death were all lower in the enzalutamide group than in the placebo group(1).

About Advanced Prostate Cancer

Prostate cancer is the most common cancer in men in developed nations and the third most prevalent cancer in the world(5). Around 300,000 new cases of prostate cancer are diagnosed in Europe each year(6).

Prostate cancer growth is primarily driven by androgen receptor (AR) signalling within the cancer cell(7). In advanced prostate cancer (APC), the cancer may continue to progress despite prior surgery, radiation therapy and conventional hormone or chemotherapy-based treatments(8).

When APC progresses despite treatment with androgen-deprivation therapy (ADT), it can be defined as castration-resistant prostate cancer (CRPC). It is thought that AR signalling continues to be an important driver of cancer growth and proliferation in CRPC(1,7).

Patients with 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(9).

About the Medivation/Astellas Collaboration

In October 2009, Medivation and Astellas entered into a global agreement to jointly develop and commercialise enzalutamide. The companies are collaborating on a comprehensive development programme that includes studies to develop enzalutamide across the full spectrum of advanced prostate cancer. Subject to receipt of regulatory approval, the companies will jointly commercialise enzalutamide in the United States and Astellas will have responsibility for commercialising enzalutamide outside the U.S.

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 becoming a global category leader in Oncology, and has several oncology compounds in development in addition to enzalutamide. For more information on Astellas Pharma Inc., please visit our website at .

About Medivation

Medivation, Inc. is a biopharmaceutical company focused on the rapid development of novel small molecule drugs 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 caregivers. For more information, please visit us at .


-- Scher H I. et al, MDV3100, an Androgen Receptor Signaling Inhibitor (ARSI), Improves Overall Survival in Patients With Prostate Cancer Post Docetaxel; Results From the Phase 3 Affirm Study. Presented at ASCO-GU, 02 February 2012

-- Astellas and Medivation, Press release: Medivation and Astellas announce Submission of a New Drug Application for Enzalutamide for the treatment of Castration-Resistant Prostate Cancer in Patients Previously treated with Chemotherapy. May 2012

-- Data presented at PROSCA, 26 June 2012

-- Scher H I. et al, Antitumour activity of MDV3100 in castration-resistant prostate cancer: a phase 1--2 study. The Lancet 2010;375(9724):1437-46

-- Beltran H. et al, Collaborative Review -- Prostate Cancer New Therapies for Castration-Resistant Prostate Cancer: Efficacy and Safety, European Urology 2011; 60(2):279-290

-- Boyle P, Ferlay J, Cancer incidence and mortality in Europe, 2004, Annals of Oncology 2005;16:481--488

-- Lonergan P E, Tindall D J, Androgen receptor signalling in prostate cancer development and progression, J Carcinog 2011;10:20

-- Nieto M, Finn S, Prostate Cancer: re-focusing on Androgen receptor signalling, Int. Journal Cell Biology 2007;39(9):1562-8

-- Yap T A, et al. The changing therapeutic landscape of castration-resistant prostate cancer, Nat. Rev. Clin. Oncol 2011;8(10):597-610

SOURCE: Astellas

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