Medivation and Astellas Announce the Phase 3 PREVAIL Trial of XTANDI▼™ (Enzalutamide) Meets Both Co-Primary Endpoints of

    Medivation and Astellas Announce the Phase 3 PREVAIL Trial of XTANDI▼™
    (Enzalutamide) Meets Both Co-Primary Endpoints of Overall Survival and
  Radiographic Progression-Free Survival in Chemotherapy-Naïve Patients with
                           Advanced Prostate Cancer

  PR Newswire

  TOKYO and SAN FRANCISCO, October 22, 2013

TOKYO and SAN FRANCISCO, October 22, 2013 /PRNewswire/ --

  *Study will be stopped early and enzalutamide 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)

Astellas Pharma Inc. and Medivation, Inc. today announced that the Independent
Data Monitoring Committee (IDMC) has informed the companies of positive
results from a planned interim analysis of the Phase 3 PREVAIL trial of XTANDI
(enzalutamide) in more than 1,700 men with metastatic castration-resistant
prostate cancer (mCRPC) that has progressed despite androgen deprivation
therapy and who have not received chemotherapy ^[i] . 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: ^[ ^i ^]

  *Patients treated with enzalutamide demonstrated a statistically
    significant overall survival advantage compared with patients receiving
    placebo (p<0.0001). Enzalutamide provided a 30% reduction in risk of death
    compared with placebo (Hazard Ratio=0.70; 95% confidence interval
    (0.59-0.83).
  *Patients treated with enzalutamide demonstrated a statistically
    significant radiographic progression-free survival advantage compared with
    patients receiving placebo (p<0.0001). Enzalutamide provided an 81%
    reduction in risk of radiographic progression or death compared with
    placebo (Hazard Ratio=0.19); 95% confidence interval (0.15-0.23).
  *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 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 intervals 13.8 months-upper limit not yet reached) in the
    enzalutamide arm and was 3.9 months (95% confidence interval, 3.7-5.4
    months) in the placebo arm.
  *Given the overall survival benefit and the observed safety profile, the
    IDMC considered the overall benefit-risk ratio to favourthe 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.

Enzalutamide is a novel, oral, once-daily androgen receptor (AR) signaling
inhibitor that inhibits multiple steps of the AR signaling pathway in three
distinct ways: It blocks androgen binding to the androgen receptors, inhibits
nuclear translocation of the AR complex and impairs association of the AR
complex with DNA, thus impairing tumour cell replication and tumour growth.
^[ii]

"These are exciting times in the treatment of mCRPC and the discovery and
development of enzalutamide represents a significant advance," said Professor
Bertrand Tombal, MD, PhD, Chairman of the Division of the Urology, Cliniques
Universitaires Saint Luc, Université Catholique de Louvain (UCL) and European
Principal Investigator for PREVAIL. "The treatment options available to men
with mCRPC have expanded significantly over the last few years, but the bottom
line is that more than 70,000 men die each year from the disease. The
registration of docetaxel was a major step towards cure but, 10 years later,
we must acknowledge that many patients never received docetaxel, as indicated
by recent Swedish data. These interim data for enzalutamide show us that its
use before docetaxel induces a dramatic improvement in time to disease
progression. These results demonstrate significant survival benefit in this
setting, which are truly unprecedented and represent an important step forward
in making this promising treatment available for men with advanced prostate
cancer across Europe, following regulatory approval."

"We are very excited about these results and the potential to offer a new
treatment option for patients with metastatic castration resistant prostate
cancer, in the pre-chemotherapy setting," saidDr Mike Holmes, Senior Medical
Director, Oncology, Astellas Pharma Europe Ltd. "There remains a high unmet
patient need for a new treatment that offers patients with advanced prostate
cancer, not only the opportunity to live for longer, but to do so with a good
quality of life. We are committed to work with our partners, Medivation, to
seek the necessary European regulatory approval for this expanded use of
enzalutamide, based on the results of PREVAIL."

Medivation and Astellas will initiate meetings with and submission to
regulatory agencies in 2014.

Enzalutamide is currently licensed in Europe for the treatment of adult men
with metastatic castration-resistant prostate cancer whose disease has
progressed on or after docetaxel therapy. ^[iii]

Notes to Editors:

About PREVAIL

The Phase 3 PREVAIL trial is a randomised, double-blind, placebo-controlled,
multi-national trial that enrolled over 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 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 approximately 516 death events. ^[iv]

About XTANDI

XTANDI (enzalutamide) is a novel, oral, once-daily androgen receptor signaling
inhibitor which works in three distinct ways: it inhibits testosterone binding
to androgen receptors, nuclear translocation of androgen receptors; and DNA
binding and activation by androgen receptors. In Europe, enzalutamide is
currently licensed for the treatment of adult men with metastatic
castration-resistant prostate cancer whose disease has progressed on or after
docetaxel therapy.

About Astellas Pharma Europe Ltd

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 pharmaceuticals. The organisation's focus is to
deliver outstanding R&D and marketing to continue growing in the world
pharmaceutical market. Astellas Pharma Europe Ltd. is responsible for 21
affiliate offices located across Europe, the Middle East and Africa, an R&D
site and three manufacturing plants. The company employs approximately 4,350
staff across these regions. For more information about Astellas Pharma Europe,
please visit http://www.astellas.eu .

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 http://www.astellas.com/en .

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
http://www.medivation.com .

About the Medivation/Astellas Collaboration

In October 2009, Medivation and Astellas entered into a global agreement to
jointly develop and commercialise enzalutamide (formerly MDV3100).The
companies are collaborating on a comprehensive development programme that
includes studies to develop enzalutamide across the full spectrum of advanced
prostate cancer. The companies are jointly commercialising enzalutamide in the
United States and Astellas will have responsibility for commercialising
enzalutamide outside the U.S, pending further regulatory authorisation. To
date, enzalutamide has been filed in Japan, Switzerland and Brazil, and has
received authorisation in the US, Canada and the EU.

References

i. Data on file: IDMC correspondence

ii. Tran C, Ouk S, Clegg NJ et al. Development of a second-generation
antiandrogen for treatment of advanced prostate cancer. Science 2009; 324
(5928): 787-790

iii. European Medicines Agency, Xtandi (enzalutamide) Summary of Product
Characteristics, 2013

iv.  http://clinicaltrials.gov/ct2/show/NCT01212991 . Last accessed 21.10.13



Job number: ENZ/13/0093/EU Date of preparation: October 2013

Contact: Contact: Mindy Dooa. Astellas Pharma Europe Ltd,
Mindy.Dooa@eu.astellas.com, +44-(0)7826-912339
 
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