Medivation, Inc. And Astellas Pharma US Announce Phase 3 Study Of Enzalutamide in Men With High-Risk, Hormone-Sensitive, Non-Metastatic Prostate Cancer That Has Recurred Following Definitive Local Therapy

SAN FRANCISCO, CA and NORTHBROOK, IL--(Marketwired - October 30, 2014) - Medivation Inc. (NASDAQ: MDVN) and Astellas today announced plans to initiate a global Phase 3 clinical trial that will evaluate the efficacy and safety of enzalutamide in patients with high-risk, hormone-sensitive, non-metastatic prostate cancer that has biochemically recurred (rising prostate-specific antigen [PSA] level) following definitive local therapy with radical prostatectomy and/or radiation therapy. Currently there is no prescription medicine specifically approved in the United States for these patients.

“It is estimated that approximately one third of men in the United States experience a rising PSA, also known as biochemical recurrence, after localized therapy for the treatment of prostate cancer(1),” said Lynn Seely, M.D., chief medical officer of Medivation, Inc. “This trial will determine if enzalutamide can delay the development of metastatic prostate cancer in high-risk men with a rapidly rising PSA. The initiation of this trial in collaboration with our partner Astellas showcases our mutual commitment to continue exploring the potential of enzalutamide in areas of significant unmet medical need.”

“Following enzalutamide’s continued positive impact on overall survival and progression-free survival versus placebo in metastatic castration-resistant prostate cancer, we are looking forward to continuing to explore the medicine’s potential impact on patients at earlier stages of the disease,” said Sef Kurstjens, M.D., Ph.D., chief medical officer of Astellas Pharma Inc. and president of Astellas Pharma Global Development, Inc.

About the Phase 3 study
The Phase 3 randomized, multi-national trial will be conducted at approximately 160 sites and is designed to enroll approximately 1,860 hormone-sensitive, non-metastatic men with biochemical recurrence following prostatectomy and/or radiation therapy that are at high risk for morbidity and mortality from prostate cancer. Patients will be randomized into three separate groups: enzalutamide plus leuprolide acetate, enzalutamide monotherapy, or placebo plus leuprolide acetate. Treatment with enzalutamide monotherapy will be open-label. Treatment with enzalutamide and placebo will be double-blind in combination with open-label leuprolide acetate.

The primary endpoint of the trial is metastasis-free survival. The trial will evaluate enzalutamide at a dose of 160 mg to be taken orally once daily. Leuprolide acetate will be given as an injection of 22.5 mg once every 12 weeks for a minimum of 3 doses. All patients will be treated for 37 weeks. Those achieving an undetectable PSA will suspend study drug(s). If the PSA rises again, study drug(s) will be restarted. Study drug treatment will then continue until disease progression.

Enzalutamide Mechanism of Action
Enzalutamide is an androgen receptor inhibitor that acts on three different steps in the androgen receptor signaling pathway.

About XTANDI® (enzalutamide) capsules
XTANDI was initially approved by the Food and Drug Administration (FDA) on August 31, 2012 for the treatment of patients with metastatic castration-resistant prostate cancer (CRPC) who have previously received docetaxel. On September 10, 2014, the FDA approved a new indication for XTANDI for the treatment of patients with metastatic 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

Reference
(1)Han M, Partin AW, Pound CR, Epstein JI, Walsh PC. Long-term biochemical disease-free and cancer-specific survival following anatomic radical retropubic prostatectomy. The 15-year Johns Hopkins experience. Urol Clin North Am. 2001 Aug;28(3):555-65.

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 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 http://www.medivation.com.

About Astellas
Astellas is a pharmaceutical company dedicated to improving the health of people around the world through provision of innovative and reliable pharmaceuticals. For more information on Astellas, please visit our website at www.astellas.us and follow us on Twitter at www.twitter.com/AstellasUS.

Forward-Looking Statements - Medivation
This press release contains forward-looking statements, including statements regarding the continued clinical development of enzalutamide and potential future progress related thereto, the therapeutic potential of enzalutamide in men with high-risk, hormone-sensitive, non-metastatic prostate cancer that has recurred following definitive local therapy, our strategy, and the continued effectiveness of, and continuing collaborative activities and benefits under, Medivation’s collaboration agreement with Astellas, which are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. 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, risks related to the timing and results of Medivation’s clinical trials, including the risk that adverse clinical trial results could alone or together with other factors result in the delay or discontinuation of some or all of Medivation’s product development activities, the risk that positive results seen in our clinical trials may not be predictive of the results of our ongoing or planned clinical trials, difficulties or delays in enrolling and retaining patients in Medivation’s clinical trials, Medivation’s dependence on the efforts of and funding by Astellas for the development of enzalutamide, the achievement of development, regulatory and commercial milestones under Medivation’s collaboration agreement with Astellas, the manufacturing of Medivation’s product candidates, the industry and competitive market, the adequacy of Medivation’s financial resources, unanticipated expenditures or liabilities, Medivation’s outstanding convertible senior notes, intellectual property matters, and 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 June 30, 2014, filed with the SEC on August 7, 2014. 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