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 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 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 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 www.medivation.com.
SOURCE Astellas Pharma US, Inc.
