`U.S. FDA Approves New Indication for the Use of XTANDI(R)
`(Enzalutamide) Capsules for Patients With Metastatic CastrationResistant
`Prostate Cancer
`Approval Based on Improved Overall Survival, Delayed Time to Radiographic Progression and an Overall
`Positive BenefitRisk Profile
`
`SAN FRANCISCO, CA and TOKYO, JAPAN (Marketwired) 09/10/14 Medivation, Inc. (NASDAQ: MDVN) and Astellas Pharma Inc.
`(TSE: 4503) announced today that the U.S. Food and Drug Administration (FDA) approved a new indication for the use of XTANDI®
`(enzalutamide) capsules to treat patients with metastatic castrationresistant prostate cancer (CRPC). This new approved use follows a
`priority review of the supplemental New Drug Application (sNDA) that was based on results of the Phase 3 PREVAIL trial.
`
`The FDA initially approved XTANDI, an oral, oncedaily androgen receptor inhibitor, in August 2012 for use in patients with metastatic
`CRPC who previously received docetaxel (chemotherapy). The new indication approves XTANDI for use in men with metastatic CRPC
`who have not received chemotherapy. Metastatic CRPC is defined as a cancer that has spread beyond the prostate gland and has
`progressed despite treatment to lower testosterone (i.e., with a gonadotropinreleasing hormone (GnRH) therapy or with removal of
`the testes).
`
`"The FDA's priority review and approval of this new indication for XTANDI now enables the use of an important therapy by patients with
`metastatic castrationresistant prostate cancer at all stages of their disease," said Sef Kurstjens, M.D., Ph.D., chief medical officer of
`Astellas Pharma Inc. and president of Astellas Pharma Global Development, Inc. "We are pleased that these patients now have XTANDI
`available as a treatment option."
`
`"All of us at Medivation extend our thanks to the clinicians and patients who participated in the PREVAIL clinical trial culminating in
`today's approval," said David Hung, M.D., founder, president and chief executive officer, Medivation, Inc. "As a company dedicated to
`the rapid development of novel therapies to treat serious diseases, we are pleased to see XTANDI approved in this important patient
`population."
`
`In the Phase 3 PREVAIL trial, men receiving XTANDI and GnRH therapy exhibited a statistically significant improvement in both overall
`survival and delayed time to radiographic progression or death as compared to those on placebo and GnRH therapy.
`
`XTANDI significantly reduced the risk of radiographic progression or death by 83% compared with placebo (HR=0.17; p <
`0.0001).
`
`XTANDI significantly reduced the risk of death by 29% compared with placebo (HR=0.71; p < 0.0001).
`
`When compared to placebo, treatment with XTANDI also delayed time to initiation of chemotherapy and time to a skeletal related
`event.
`
`The safety profile for XTANDI was updated to reflect data from both the AFFIRM and PREVAIL Phase 3 trials.
`
`Seizure occurred in 0.9% of patients receiving XTANDI who previously received docetaxel and 0.1% of patients who were
`chemotherapynaive.
`
`The most common adverse reactions ( ≥ 10%) that occurred more commonly ( ≥ 2% over placebo) in the XTANDItreated
`patients from the two randomized clinical trials 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.
`
`"Enzalutamide has been studied and is approved for patients with metastatic prostate cancer that is resistant to primary hormonal
`therapy, a disease state we call castrationresistant prostate cancer. In this setting, enzalutamide has been shown to extend overall
`survival and significantly delay the progression of prostate cancer," said Tomasz M. Beer, M.D., F.A.C.P., coprincipal investigator of the
`PREVAIL study, deputy director of the Knight Cancer Institute and professor of medicine at Oregon Health & Science University.
`"Furthermore, in the PREVAIL trial, the median time to initiating chemotherapy was delayed by 17 months with enzalutamide
`treatment as compared to placebo, so the result is a meaningful period of time during which men have their disease controlled without
`the need for chemotherapy."
`
`A variation application to amend the European Marketing Authorization Application based on the results of PREVAIL was validated for
`review by the European Medicines Agency on April 24, 2014.
`
`The approval of this new indication for XTANDI triggers $90 million in milestone payments to Medivation under its collaboration
`agreement with Astellas.
`
`Enzalutamide Mechanism of Action
`Enzalutamide is an androgen receptor inhibitor that acts on three different steps in the androgen receptor signaling pathway.
`
`7/24/2015 U.S. FDA Approves New Indication for the Use of XTANDI(R) (Enzalutamide) Capsules for Patients With Metastatic CastrationResistant Prostate Can…
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`About XTANDI® (enzalutamide) capsules
`XTANDI (enzalutamide) was approved by the FDA on September 10, 2014 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 castrationresistant 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 chemotherapynaïve 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 XTANDItreated 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 34) and in 6% of patients treated with placebo (0.5% Grade 34). The incidence of Grade 1‐4 thrombocytopenia was 6%
`of patients treated with XTANDI (0.3% Grade 34) and 5% of patients on placebo (0.5% Grade 34). Grade 14 elevations in ALT
`occurred in 10% of patients treated with XTANDI (0.2% Grade 34) and 16% of patients treated with placebo (0.2% Grade 34).
`Grade 14 elevations in bilirubin occurred in 3% of patients treated with XTANDI (0.1% Grade 34) and 2% of patients treated
`with placebo (no Grade 34).
`
`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
`
`Medivation Conference Call Information
`Medivation will host a live conference call and webcast on September 11, 2014 at 5:30 am PT. To access the call, please dial 877303
`2523 from the United States or +12532371755 internationally. Individuals may access the live audio webcast by visiting
`www.medivation.com and going to the Investor Relations section. A replay of the webcast will be available on the Company's website
`(www.medivation.com) for 30 days following the live event.
`
`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.
`
`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 http://www.medivation.com.
`
`About the Astellas/Medivation Collaboration
`
`7/24/2015 U.S. FDA Approves New Indication for the Use of XTANDI(R) (Enzalutamide) Capsules for Patients With Metastatic CastrationResistant Prostate Can…
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`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.
`
`Forward Looking Statements
`This press release contains forwardlooking statements that are made pursuant to the safe harbor provisions of the federal securities
`laws, including statements regarding the potential benefit of XTANDI in the indicated patient population. Any statements contained in
`this press release that are not statements of historical fact may be deemed to be forwardlooking statements. Forwardlooking
`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 in the new indication, as well as other risks detailed in Medivation's filings with the Securities and Exchange Commission,
`including its quarterly report on Form 10Q for the quarter ended June 30, 2014, filed on August 7, 2014 with the SEC. You are
`cautioned not to place undue reliance on the forwardlooking statements, which speak only as of the date of this release. Medivation
`disclaims any obligation or undertaking to update or revise any forwardlooking statements contained in this press release.
`
`Astellas Contact:
`Tyler Marciniak
`Director, Communications and Advocacy
`(847) 7367145
`Email Contact
`
`Medivation Contact:
`Rick Bierly
`Chief Financial Officer
`(415) 5433470
`
`Anne Bowdidge
`Senior Director, Investor Relations
`(650) 2186900
`
`Source: Medivation
`
`News Provided by Acquire Media
`
`Copyright 2015 Medivation, Inc.
`
`7/24/2015 U.S. FDA Approves New Indication for the Use of XTANDI(R) (Enzalutamide) Capsules for Patients With Metastatic CastrationResistant Prostate Can…
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