Astellas Announces Marketing Authorisation Application for XTANDI™ (enzalutamide) for Chemotherapy-Naïve Metastatic Prostate

      Astellas Announces Marketing Authorisation Application for XTANDI™
       (enzalutamide) for Chemotherapy-Naïve Metastatic Prostate Cancer

  PR Newswire

  TOKYO, April 3, 2014

TOKYO, April 3, 2014 /PRNewswire/ --

Astellas Pharma Inc. (TSE:4503) today announces the submission of a variation
to amend the Marketing Authorisation Application for XTANDI ^™ (enzalutamide)
capsules for the treatment of adult men with metastatic castration-resistant
prostate cancer (mCRPC) who are asymptomatic or mildly symptomatic after
failure of androgen deprivation therapy and in whom chemotherapy is not yet
clinically indicated.Enzalutamide is currently approved in Europe for the
treatment of adult men with mCRPC whose disease has progressed on or after
docetaxel chemotherapy. ^[i]

This announcement follows presentation of the Phase III data for the PREVAIL
trial at the American Society of Clinical Oncology (ASCO) 2014 Genitourinary
(GU) Cancers Symposium in San Francisco on Thursday, January 30, 2014. ^[ii]

In the Phase III PREVAIL trial, treatment with enzalutamide showed a
statistically significant overall survival benefit compared with placebo, with
enzalutamide reducing the risk of death by 29% (HR=0.71; p<0.0001), compared
with placebo. ^[ ^ii ^] Treatment with enzalutamide also significantly reduced
the risk of radiographic progression or death by 81% compared with placebo
treatment (HR=0.19; p<0.0001). ^[ ^ii ^] Men taking enzalutamide experienced a
17-month delay in the time to initiation of chemotherapy compared with men
taking placebo (28.0 months versus 10.8 months; HR=0.35; p<0.0001). ^[ ^ii ^]
The study also concluded that enzalutamide was generally well tolerated by
patients and met all secondary endpoints. ^[ ^ii ^]

Prostate cancer is the most common cancer in men in Europe, accounting for
over 20% of all cancer diagnoses (excluding non-melanoma skin cancer) and is
the third most common cause of cancer death in Europe. ^[iii] Up to 40% of men
with prostate cancer develop metastatic disease and a high number of these men
eventually fail androgen deprivation treatment, which is called
castration-resistant prostate cancer (CRPC). ^[iv]

"Oncology is a growing area of focus for Astellas, and we are committed to
developing and bringing to market medicines which meet current unmet medical
needs," said Dr Ayad Abdulahad, Senior Vice President, Medical Affairs &
Health Economics, Astellas Pharma Europe Ltd. "We will continue to work with
our partner, Medivation, to seek the necessary European regulatory
approvalfor Xtandi, that will allow for its use amongst patients who have not
received chemotherapy for their advanced prostate cancer."

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-naïve
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.

About XTANDI ^™ ^

Xtandi is a novel, oral, once-daily androgen receptor signalling inhibitor.
Xtandi directly targets the androgen receptors (AR) and exerts its effects on
all three steps of AR signalling pathway:

  *Blocks androgen binding ^[v] 

       *Androgen binding induces a conformational change that triggers
         activation of the receptor ^[vi] 

  *Prevents nuclear translocation ^[ ^v ^]

       *Transit of the AR to the nucleus is an essential step in AR-mediated
         gene regulation ^[ ^vi ^]

  *Impairs DNA binding ^[ ^v ^]

       *Binding of the AR to the DNA is essential for modulation of gene
         expression ^[ ^vi ^]

Xtandi was approved by the FDA on August 31, 2012 and is indicated for the
treatment of adult men with mCRPC who have previously received docetaxel

Xtandi is currently licensed in Europe for the treatment of adult men with
mCRPC whose disease has progressed on or after docetaxel therapy. ^[ ^i ^]
Marketing authorisation was granted by the European Commission on June 21,

In March 2014, Astellas and Medivation submitted a supplemental new drug
application for Xtandi for chemotherapy-naïve advanced prostate cancer to the
US Food and Drug Administration.

Important Safety Information for XTANDI ^™ ^

For important Safety Information for Xtandi please see the full Summary of
Product Characteristics at:

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 organisation 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 .

About the Astellas / Medivation Collaboration 

InOctober 2009,Medivationand 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
inthe United Statesand Astellas will have responsibility for manufacturing
and all additional regulatory filings globally, as well as commercializing
Xtandi outsidethe United States.

i. European Medicines Agency, XTANDI, (enzalutamide) Summary of Product
Characteristics, 2013

ii. Beer T, et al. Enzalutamide Decreases Risk of Death and Delays Progression
in Phase 3 Trial of Men with Metastatic Prostate Cancer. Presentation ASCO GU

iii. Ferlay J, Shin HR, Bray F et al. Globocan 2008 v2.0, cancer incidence and
mortality worldwide. IARC CancerBase No. 10 [Internet]. Lyon, France:
International Agency for Research on Cancer 2010. Available from: . Last accessed March 2014

iv. Beltran H, Beer TM, Carducci MA et al. New therapies for
castration-resistant prostate cancer: Efficacy and safety. Eur Urol 2011; 60
(2): 279-290

v. Tran C, et al. Development of a second-generation antiandrogen for
treatment of advanced prostate cancer. Science 2009;324:787-790 

vi. Hu R, Denmeade SR and Luo J. Molecular processes leading to aberrant
androgen receptor signaling and castration resistance in prostate cancer.
Expert Rev Endocrinol Metab 2010; 5 (5): 753-764

vii. U.S. Food and Drug Administration. Enzalutamide (XTANDI Capsules).
Available from: . Last
accessed March 2014

Contact: Astellas Contacts: Mindy Dooa, Communications Director,
+44(0)7826-912339; Katy Pogson, Red Door Communications, +44(0)7941-418962;
Medivation Contacts: Anne Bowdidge, Senior Director, Investor Relations,
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