Astellas and Medivation Receive Priority Review from FDA for XTANDI®
(Enzalutamide) Capsules In Chemotherapy-Naive Advanced Prostate Cancer
TOKYO and SAN FRANCISCO, May 6, 2014
TOKYO and SAN FRANCISCO, May 6, 2014 /PRNewswire/ --Astellas Pharma Inc.
(TSE: 4503) and Medivation Inc. (NASDAQ: MDVN) today announced that the U.S.
Food and Drug Administration (FDA) has accepted for filing the supplemental
New Drug Application (sNDA) to extend the indication for XTANDI®
(enzalutamide) capsules for the treatment of men with metastatic
castration-resistant prostate cancer (mCRPC) who have not received
chemotherapy. This sNDA application was granted Priority Review designation
with a stated FDA Prescription Drug User Fee Act (PDUFA) review date of
September 18, 2014. 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-naïve
mCRPC patients. A variation application to amend the European Marketing
Authorization Application was submitted to the European Medicines Agency on
April 2, 2014.
The FDA's acceptance of the sNDA triggers a milestone payment to Medivation
under its collaboration agreement with Astellas.
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® (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
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
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 www.astellas.com/en.
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.
About the Astellas/Medivation Collaboration
In October 2009, Astellas and Medivation 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.
SOURCE Astellas Pharma Inc.
Contact: Astellas Contact: Tyler Marciniak, Director, Communications and
Advocacy, (847) 736-7145, email@example.com; Medivation Contact:
Anne Bowdidge, Senior Director, Investor Relations, (650) 218-6900
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