-Study appears in June 1 online edition-
TORONTO, June 1, 2014 /CNW/ - Astellas Pharma Canada, Inc., the Canadian
subsidiary of Tokyo-based Astellas Pharma, Inc. (Tokyo: 4503) today
announced the publication in the New England Journal of Medicine of the results from the Phase 3 PREVAIL trial, an international,
randomized, double-blind, placebo-controlled clinical study of
enzalutamide in men with chemotherapy-naïve metastatic
castration-resistant prostate cancer (mCRPC) who have failed androgen
deprivation therapy and have few or no symptoms. The paper, "Benefit of
Enzalutamide in Men with Chemotherapy-Naïve Metastatic Prostate
Cancer," appears in the June 1 online issue and the companies
anticipate a publication in a future print issue of the Journal.
"The PREVAIL study offers us critical insight into the management of
metastatic prostate cancer prior to treatment with chemotherapy," said
Dr. Fred Saad, Professor and Chief of Urology, University of Montreal
Hospital Center and a PREVAIL investigator. "The reported results will
undoubtedly help the medical community better understand the potential
use of enzalutamide to prolong the lives of men with metastatic
The safety and efficacy of enzalutamide in men with chemotherapy-naïve
mCRPC has not yet been evaluated by Health Canada. In Canada,
arrangements are currently underway for submission of a Supplemental
New Drug Submission (sNDS) later this year, based on the PREVAIL study
results. A supplemental New Drug Application (sNDA) based on the
PREVAIL results received a priority review designation from the U.S.
Food and Drug Administration (FDA). The Prescription Drug User Fee Act
(PDUFA) goal date is September 18, 2014. A variation application to
amend the European Marketing Authorization Application based on the
results of PREVAIL was validated for review by the European Medicines
Agency on April 24, 2014.
"At Astellas we are proud to support research that helps advance the
treatment of metastatic prostate cancer," says Michael Tremblay,
President, Astellas Pharma Canada, Inc. "As a company we remain
committed to continuing to address the challenges of treating this
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 Canada, the United States, Europe, Australia,
Russia, Israel and Asia including Japan. The trial enrolled patients
with chemotherapy-naïve metastatic prostate cancer whose disease
progressed on androgen deprivation therapy (i.e., a luteinizing
hormone-releasing hormone (LHRH) therapy 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.
In the PREVAIL trial, men treated with enzalutamide demonstrated a statistically significant delay in cancer
progression and reduction in the risk of death compared with placebo.
Enzalutamide reduced the risk of radiographic progression or death by
81% (HR=0.19; p 0.0001), compared with placebo. The rate of
radiographic progression-free survival at 12 months of follow up was
65% among patients treated with enzalutamide, as compared with 14%
among patients receiving placebo.
Enzalutamide reduced the risk of death by 29% (HR=0.71; p 0.0001),
compared with placebo. A total of 626 patients (72%) in the
enzalutamide group, as compared with 532 patients (63%) in the placebo
group, were alive at the September 16, 2013 data cutoff date.
The most common clinically relevant adverse events associated with
enzalutamide treatment as compared with placebo-treated patients in the
PREVAIL trial included fatigue, hot flush and hypertension;
hypertension was observed in 13.4% of enzalutamide versus 4.1% of
placebo-treated patients. Grade 3 or higher cardiac adverse events were
reported in 2.8% of enzalutamide versus 2.1% of placebo-treated
patients. One patient experienced a seizure in each treatment group.
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
About XTANDI® (enzalutamide) capsules
XTANDI was approved by Health Canada on May 30, 2013 and is indicated
for the treatment of patients with metastatic castration-resistant
prostate cancer in the setting of medical or surgical castration who
have received docetaxel therapy.
Important Safety Information for XTANDI (from the approved Product
The safety and efficacy of XTANDI has not been established for patients
under 18 years of age
Women who are or may become pregnant, or who are lactating
Most serious warnings and precautions
Seizures: increased risk. Seizure risk may be dose dependent with a greater risk
at daily doses higher than 160 mg. There is no clinical trial
experience re-administering XTANDI to patients who experienced seizures
Other relevant warnings and precautions:
Drug contains sorbitol; avoid in patients with hereditary fructose
Associated with neuropsychiatric adverse events; advise on risk of
engaging in activities where mental impairment or sudden loss of
consciousness could cause serious harm
Induces CYP3A4, CYP2C9, and CYP2C19; avoid concomitant use or dose
adjust with drugs with a narrow therapeutic range that are substrates
of these enzymes or UGT1A1; monitoring may be required (eg, INR for
Avoid concomitant use or adjust XTANDI dose with strong CYP2C8 or
Safety not established in patients with clinically significant
Associated with QTc prolongation; monitor ECG and electrolytes for
patients at risk
Associated with blood pressure increases; monitor periodically
Associated with non-pathological bone fractures
Advise on use of contraception
May affect male fertility (based on animal studies)
Not recommended in patients with severe hepatic impairment
Caution is advised in patients with severe renal impairment or end-stage
For Full Prescribing Information for XTANDI (enzalutamide) capsules,
please visit www.astellas.ca/products.
About Astellas Pharma Canada, Inc.
Astellas Pharma Canada, Inc., headquartered in Markham, ON, is a
Canadian affiliate of Tokyo-based Astellas Pharma Inc. Astellas is a
pharmaceutical company dedicated to improving the health of people
around the world through the provision of innovative and reliable
pharmaceutical products. The organization is committed to becoming a
global category leader in focused areas by combining outstanding R&D
and marketing capabilities. In Canada, Astellas has an intense
commercial focus on five therapeutic areas - Urology, Immunology,
Infectious Disease, Dermatology and Oncology.
For more information about Astellas Pharma Canada, Inc., please visit
the corporate website: www.astellas.ca.
SOURCE: Astellas Pharma Canada, Inc.
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