Medivation and Astellas Announce the Phase 3 PREVAIL Trial of XTANDI?(TM) (Enzalutamide) Meets Both Co-Primary Endpoints of Overall Survival and Radiographic Progression-Free Survival in Chemotherapy-

Tokyo And San Francisco (ots/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 favour 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.

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," said Dr
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

ots Originaltext: Astellas Pharma Europe Limited
Im Internet recherchierbar: http://www.presseportal.de

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