Medivation and Astellas Announce the Phase 3 PREVAIL Trial of Enzalutamide Meets Both Co-Primary Endpoints of Overall Survival

Medivation and Astellas Announce the Phase 3 PREVAIL Trial of Enzalutamide 
Meets Both Co-Primary Endpoints of Overall Survival and
Radiographic Progression-Free Survival in Chemotherapy-Naive Patients
With Advanced Prostate Cancer 
Study Will Be Stopped Early and Enzalutamide Will Be Offered to All
Qualified Study Participants; 30% Reduction in the Risk of Death,
Hazard Ratio=0.70 (p < 0.0001); 81% Reduction in the Risk of
Radiographic Progression or Death, Hazard Ratio=0.19 (p < 0.0001);
Medivation to Hold Conference Call at 8:30 a.m. Eastern Time Today 
SAN FRANCISCO, CA and TOKYO, JAPAN -- (Marketwired) -- 10/22/13 -- 
Medivation, Inc. (NASDAQ: MDVN) and Astellas Pharma Inc. (TSE: 4503)
today announced that the Independent Data Monitoring Committee (IDMC)
has informed the companies of positive results from a planned interim
analysis of the global Phase 3 PREVAIL trial of enzalutamide in more
than 1,700 men with metastatic prostate cancer that has progressed
despite androgen deprivation therapy and who have not yet received
chemotherapy. Given the observed benefits in the trial's co-primary
endpoints of overall survival and radiographic progression-free
survival, and considering the observed safety profile, the IDMC
concluded enzalutamide demonstrated a favorable benefit-risk ratio.
The IDMC recommended the study be stopped and patients treated with
placebo be offered enzalutamide. Additional data from the Phase 3
PREVAIL results, including safety data, will be submitted for
presentation at an upcoming medical conference.  
The IDMC informed the companies of the following results: 


 
--  Patients treated with enzalutamide demonstrated a statistically
    significant overall survival advantage compared with patients
    receiving placebo (p Patients treated with enzalutamide demonstrated a
    statistically significant radiographic progression-free survival
    advantage compared with patients receiving placebo (p The percentage
    of patients alive in the enzalutamide arm was 72% as compared with 65%
    in the placebo arm at the time of the interim analysis data cut-off
    date. Treatment with enzalutamide resulted in a calculated point
    estimate for median overall survival of 32.4 months (95% confidence
    interval, 31.5 months-upper limit 
not yet reached) versus 30.2 months
    (95% confidence interval, 28.0 months-upper limit not yet reached) for
    patients receiving placebo. Because the trial will be stopped early
    with the majority of patients still alive, the estimated median
    survivals are not as precise as the hazard ratio. The hazard ratio
    takes into account available information about the trial endpoint from
    all patients whereas the median is a single point estimate of a much
    smaller number of patients at risk.
--  The median radiographic progression-free survival was not yet reached
    (95% confidence interval, 13.8 months-upper limit not yet reached) in
    the enzalutamide arm and was 3.9 months (95% confidence interval,
    3.7-5.4) in the placebo arm.
--  Given the overall survival benefit and the observed safety profile,
    the IDMC considered the overall benefit-risk ratio to favor the
    enzalutamide arm and recommended unequivocally that patients receiving
    placebo be offered treatment with enzalutamide.

  
Of the 1,715 patients treated in the blinded PREVAIL study, two
patients were reported by investigators to have had a seizure event.
The full analysis of the safety data will become available upon final
database lock and unblinding. 
"To my knowledge, the benefits in overall survival and radiographic
progression-free survival reported in today's PREVAIL trial results
are unprecedented in this patient population," said Tomasz M. Beer,
M.D., F.A.C.P., professor of medicine and deputy director of the
Knight Cancer Institute at Oregon Health & Science University, and
the co-principal investigator of the PREVAIL study.  
"Achieving statistically-significant and clinically meaningful
results in both co-primary endpoints -- overall survival and
radiographic progression-free survival -- is an important outcome for
patients and we are excited by the results of the Phase 3 PREVAIL
trial," said David Hung, M.D., founder, president and CEO,
Medivation. "I extend my sincere thanks to the patients, physicians,
study teams and other collaborators around the world, who have been
instrumental in helping us achieve this important milestone." 
"We are very pleased about these results and will work closely with
Medivation to pursue an expanded indication for enzalutamide," said
Sef Kurstjens, M.D., Ph.D., Chief Medical Officer of Astellas. "We
are committed to being at the forefront of the fight against prostate
cancer by providing patients with treatment options to help them
manage their disease."  
Medivation and Astellas will initiate meetings with and submissions
to regulatory agencies beginning in early 2014.  
About PREVAIL
 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 metastatic prostate cancer
whose disease progressed despite treatment with androgen deprivation
therapy and had not yet received chemotherapy. The co-primary
endpoints of the trial are 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. Targeted enrollment was completed in May 2012 and the
interim analysis was pre-specified after 516 events (patient deaths). 
Conference Call Information
 Medivation will host a conference call
today at 8:30 a.m. Eastern Time. To access the call, please dial
(877) 303-2523 from the United States or +1 (253) 237-1755
internationally. In addition, the live conference call is being
webcast and can be accessed on the "Events and Presentations" page of
the "Investor Relations" section of the Company's website at
www.medivation.com. 
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 (&#8805;
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 for XTANDI (enzalutamide) capsules,
please visit www.XtandiHCP.com. 
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 and in breast cancer. The companies are jointly
commercializing enzalutamide in the United States and Astellas has
responsibility for commercializing enzalutamide outside the United
States, pending further regulatory approval.  
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. 
Forward-Looking Statements
 This press release contains
forward-looking statements, including statements regarding the
continued clinical development of enzalutamide and potential future
progress related thereto, 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 potential
regulatory approval and commercialization of enzalutamide, the
progress, 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
and the risk that life-prolonging treatments could prevent ongoing or
planned enzalutamide trials from succeeding or could reduce any
potential survival benefit that may be shown in these trials even if
they do succeed, difficulties or delays in enrolling and retaining
patients in Medivation's clinical trials, including as a result of
the availability of competing treatments or clinical trials of
competing drugs for the same indication, 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, 2013, filed with
the SEC on August 8, 2013. 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. 
Medivation Contacts: 
Patrick Machado 
Chief Business & Financial Officer 
(415) 829-4101  
Anne Bowdidge 
Senior Director, Investor Relations 
(650) 218-6900  
Astellas Contacts:
Jenny Kite 
Corporate Communications 
(847) 682-4530 
Mike Beyer
Sam Brown, Inc (media for both companies)
(773) 463-4211  
 
 
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