Astellas and Medivation Receive Priority Review From FDA for XTANDI(R) (Enzalutamide) Capsules in Chemotherapy-Naive Advanced

Astellas and Medivation Receive Priority Review From FDA for XTANDI(R) 
(Enzalutamide) Capsules in Chemotherapy-Naive Advanced
Prostate Cancer 
SAN FRANCISCO, CA and TOKYO, JAPAN -- (Marketwired) -- 05/06/14 -- 
Medivation, Inc. (NASDAQ: MDVN) and Astellas Pharma Inc. (TSE: 4503)
today announced that the U.S. Food and Drug Administration (FDA) has
accepted for filing the supplemental New Drug Application (sNDA) to
extend the indication for XTANDI(R) (enzalutamide) capsules for the
treatment of men with metastatic castration-resistant prostate cancer
(mCRPC) who have not received chemotherapy. This sNDA application was
granted Priority Review designation with a stated FDA Prescription
Drug User Fee Act (PDUFA) review date of September 18, 2014. XTANDI
is currently approved for the treatment of patients with mCRPC who
have previously received docetaxel chemotherapy. 
The sNDA application is based on the results from the Phase 3 PREVAIL
trial evaluating XTANDI as compared to placebo in more than 1,700
chemotherapy-naive mCRPC patients. A variation application to amend
the European Marketing Authorization Application was submitted to the
European Medicines Agency on April 2, 2014.  
The FDA's acceptance of the sNDA triggers a milestone payment to
Medivation under its collaboration agreement with Astellas. 
About the PREVAIL Trial 
 The Phase 3 PREVAIL trial is a randomized,
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 Asian countries including
Japan. The trial enrolled patients with chemotherapy-naive metastatic
prostate cancer whose disease progressed on a luteinizing
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.  
Enzalutamide Mechanism of Action 
 Enzalutamide is an androgen
receptor inhibitor that acts on different steps in the androgen
receptor signaling pathway. Enzalutamide has been shown to
competitively inhibit androgen binding to androgen receptors, and
inhibit androgen receptor nuclear translocation and interaction with
DNA.  
About XTANDI(R) (enzalutamide) capsules 
 XTANDI was approved by the
FDA on August 31, 2012 and is indicated for the treatment of patients
with metastatic castration-resistant prostate cancer (mCRPC) who have
previously received docetaxel.  
Important Safety Information for XTANDI (from the approved
prescribing information) 
 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 versus 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 for XTANDI (enzalutamide) capsules,
please visit www.XtandiHCP.com.  
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 families. For more
information, please visit us at www.medivation.com.  
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 the Astellas/Medivation Collaboration
 In October 2009,
Astellas and Medivation 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 will
have responsibility for manufacturing and all additional regulatory
filings globally, as well as commercializing XTANDI outside the
United States.  
Medivation Contact: 
Anne Bowdidge 
Senior Director, Investor Relations 
(650) 218-6900  
Astellas Contact:
Tyler Marciniak 
Director, Communications and Advocacy
(847) 736-7145
tyler.marciniak@astellas.com 
 
 
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