Astellas Announces European Regulatory Submission For XTANDI® (enzalutamide) Capsules For Chemotherapy-Naive Metastatic

 Astellas Announces European Regulatory Submission For XTANDI® (enzalutamide)
          Capsules For Chemotherapy-Naive Metastatic Prostate Cancer

PR Newswire

TOKYO and SAN FRANCISCO, April 3, 2014

TOKYO and SAN FRANCISCO, April 3, 2014 /PRNewswire/ -- Astellas Pharma Inc.
(TSE:4503) and Medivation Inc. (NASDAQ: MDVN) today announced the submission
of a variation to amend the European Marketing Authorization 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. ^ XTANDI is currently
approved in Europe for the treatment of adult men with mCRPC whose disease has
progressed on or after docetaxel chemotherapy.

The European 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.

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.

XTANDI Mechanism of Action

XTANDI is an androgen receptor inhibitor that acts on different steps in the
androgen receptor signaling pathway. XTANDI has been shown to competitively
inhibit androgen binding to androgen receptors, and inhibit androgen receptor
nuclear translocation and interaction with DNA.

About XTANDI® (enzalutamide) capsules

XTANDI is currently licensed in Europe for the treatment of adult men with
mCRPC whose disease has progressed on or after docetaxel therapy. Marketing
authorization was granted by the European Commission on June 21, 2013.

In March 2014, Astellas and Medivation submitted a supplemental new drug
application for XTANDI for the treatment of men with metastatic
castration-resistant prostate cancer (mCRPC) who have not received
chemotherapy to the U.S. Food and Drug Administration.

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 U.S. prescribing

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

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

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

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

About the Astellas/Medivation 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 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.

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

SOURCE Astellas Pharma US, Inc.

Contact: Astellas Contacts: Mindy Dooa, Communications Director (Europe), +44
(0) 7826 912339, Tyler Marciniak, Communications Director (U.S.), (917) 650
1523 or Medivation Contact: Anne Bowdidge, Senior Director, Investor
Relations, (650) 218-6900
Press spacebar to pause and continue. Press esc to stop.