Daily News: Disease

XTANDI(TM) (Enzalutamide) Authorized in the European Union for Advanced Prostate Cancer

Business Wire

06-24-13

--Enzalutamide authorized in European Union for the treatment of adult men with metastatic castration-resistant prostate cancer whose disease has progressed on or after docetaxel therapy--

CHERTSEY, England & SAN FRANCISCO--(BUSINESS WIRE)-- Astellas Pharma Europe Ltd., the European Headquarters of Tokyo-based Astellas Pharma Inc. (TSE:4503), and Medivation, Inc. (Nasdaq: MDVN) announced that following the regulatory review process by the European Medicines Agency (EMA) and a positive opinion from the Committee for Medicinal Products for Human Use on April 25, 2013, the European Commission (EC) has granted the marketing authorization for XTANDI(TM) (enzalutamide) capsules for the treatment of adult men with metastatic castration-resistant prostate cancer whose disease has progressed on or after docetaxel therapy.

"This is a major development in prostate cancer therapeutics that will provide an important new treatment option for patients with advanced prostate cancer following chemotherapy," said Professor Johann de Bono, Professor of Experimental Cancer Medicine at The Institute of Cancer Research, London, and Consultant Medical Oncologist at The Royal Marsden NHS Foundation Trust.

Professor de Bono, who is also Head of the Drug Development Unit, a joint facility between The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, located at The Royal Marsden, added: "Enzalutamide, an oral drug, improves the quality of life and survival time for patients who have an advanced form of this common disease and is generally well tolerated."

The EC grant of the marketing authorization applies in all European Union (EU) Member States, as well as in the European Economic Area (EEA) countries Iceland, Liechtenstein and Norway.

Dr. Erik Briers, Executive Director, European Cancer Patient Coalition (ECPC) and member of the strategic committee of Europa Uomo comments: "Unfortunately prostate cancer can evolve into a life threatening castration resistant metastatic condition where treatment options are needed because all patients are not identical. A new treatment such as enzalutamide is one more option that will give selected patients a new chance if other options fail. Patients with advanced prostate cancer are very concerned about their quality of life, so they favor treatments with fewer side effects. Enzalutamide has been shown to be generally well tolerated."

The European Commission approval triggers a $15 million milestone payment to Medivation under its collaboration with Astellas, which is reflected in Astellas' current fiscal year (from 1st April 2013 to 31st March 2014) financial forecast.

About Enzalutamide

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

The EU approval is based on results from the Phase 3 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 Phase 3 AFFIRM trial was a randomized, 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 docetaxel-based chemotherapy.

Enzalutamide was approved by the U.S. 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) and launched in the U.S. in September 2012. On May 30, 2013, Health Canada approved XTANDI (enzalutamide) capsules for the treatment of patients with metastatic castration-resistant prostate cancer in the setting of medical or surgical castration who have received docetaxel therapy. Marketing applications for XTANDI have also been submitted in Australia, Brazil, Japan, South Korea, Switzerland and Brazil.

Advanced prostate cancer is defined as cancer that has spread outside of the prostate to other areas of the body (metastasized). A high number of men with advanced prostate cancer eventually develop a resistance to androgen deprivation treatment, which is called castration-resistant prostate cancer (CRPC). Around 10-20% of patients with prostate cancer present at an advanced state, and up to 40% of men diagnosed with prostate cancer will eventually develop advanced disease.

Important US Label Safety Information for XTANDI

Contraindications- XTANDI can cause fetal harm when administered to a pregnant woman based on its mechanism of action. XTANDI is not indicated for use in women. XTANDI is contraindicated in women who are or may become pregnant.

Warnings and Precautions- In the randomized clinical trial, seizure occurred in 0.9% of patients on XTANDI. No patients on the placebo arm experienced seizure. Patients experiencing a seizure were permanently discontinued from therapy. All seizures resolved.

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. Because of the risk of seizure associated with XTANDI use, patients should be advised of the risk of engaging in any activity where sudden loss of consciousness could cause serious harm to themselves or others.

Adverse Reactions- The most common adverse drug reactions ( >= 5%) reported in patients receiving XTANDI in the randomized clinical trial were asthenia/fatigue, back pain, diarrhea, 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 1-4 neutropenia occurred in 15% of XTANDI patients (1% Grade 3-4) and in 6% on placebo (no Grade 3-4). Grade 1-4 elevations in bilirubin occurred in 3% of XTANDI patients and 2% on placebo. One percent of XTANDI patients compared to 0.3% on placebo died from infections or sepsis. Falls or injuries related to falls occurred in 4.6% of XTANDI patients vs 1.3% on 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. Grade 1 or 2 hallucinations occurred in 1.6% of XTANDI patients and 0.3% on placebo, with the majority on opioid-containing medications at the time of the event.

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 can 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, please visit www.XtandiHCP.com.

About Astellas Pharma Europe

Astellas Pharma Europe Ltd., located in the UK, is the European Headquarters 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. As a global company, Astellas is committed to combining outstanding research and development (R&D) and marketing capabilities to continue to grow in the world pharmaceutical market. Astellas Pharma Europe Ltd. manages 21 affiliate offices located across Europe, the Middle East and Africa. In addition, the Company has an R&D site and three manufacturing plants in Europe. The company employs approximately 4,300 staff across these regions. For more information about Astellas Pharma Europe, please visit http://www.astellas.eu.

About Medivation

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. Medivation aims to transform the treatment of these diseases and offer hope to critically ill patients and their families. For more information, please visit us at www.medivation.com.

This press release contains forward-looking statements that are made pursuant to the safe harbor provisions of the federal securities laws, including statements regarding the expected commercialization of XTANDI. Any statements contained in this press release that are not statements of historical fact may be deemed to be forward-looking statements. Forward-looking statements involve risks and uncertainties that could cause Medivation's actual results to differ significantly from those projected, including, without limitation, the risk that unanticipated developments could delay or prevent the launch and commercialization of XTANDI, as well as other risks detailed in Medivation's filings with the Securities and Exchange Commission, including its quarterly report on Form 10-Q for the quarter ended March 31, 2013, filed on May 10, 2013 with the SEC. You are cautioned not to place undue reliance on the forward-looking statements, which speak only as of the date of this release. Medivation disclaims any obligation or undertaking to update or revise any forward-looking statements contained in this press release.

Photos/Multimedia Gallery Available: http://www.businesswire.com/multimedia/home/20130623005059/en/

Medivation Contacts: Patrick Machado Chief Business & Financial Officer (415) 829-4101 or Anne Bowdidge Senior Director, Investor Relations (650) 218-6900 or Astellas Contacts: Jenny Kite Corporate Communications (847) 682-4530 or Mike Beyer Sam Brown Inc. (media for both companies) (773) 463-4211

Source: Astellas Pharma Europe

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