Astellas and Medivation Submit Supplemental New Drug Application for XTANDI (Enzalutamide) for Chemotherapy-Naive Advanced

Astellas and Medivation Submit Supplemental New Drug Application for XTANDI 
(Enzalutamide) for Chemotherapy-Naive Advanced Prostate Cancer 
TOKYO, JAPAN and SAN FRANCISCO, CA -- (Marketwired) -- 03/18/14 -- 
Astellas Pharma Inc. (TSE: 4503) and Medivation Inc. (NASDAQ: MDVN)
today announced the submission of a supplemental New Drug Application
(sNDA) to the U.S. Food and Drug Administration (FDA) seeking
approval of XTANDI(R) (enzalutamide) capsules for the treatment of
men with metastatic castration-resistant prostate cancer (mCRPC) who
have not received chemotherapy. XTANDI is currently approved for the
treatment of patients with mCRPC who have previously received
docetaxel chemotherapy. 
The sNDA 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. The marketing authorization
application is expected to be submitted to the European Medicines
Agency later this year.  
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-naive 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.  
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 (≥
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 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 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 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. 
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. 
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 
(224) 204-5405 
Mike Beyer
Sam Brown, Inc (media for both companies) 
(773) 463-4211  
 
 
Press spacebar to pause and continue. Press esc to stop.