New England Journal of Medicine Publishes Results from Phase 3 PREVAIL Trial of Enzalutamide in Men with Chemotherapy-Naïve Metastatic Prostate Cancer Progressing on Androgen Deprivation Therapy

-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 prostate cancer."

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 devastating disease."

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 with DNA.

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 Monograph)

Clinical use

• The safety and efficacy of XTANDI has not been established for patients under 18 years of age

Contraindication

• 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 intolerance
• 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 warfarin/acenocoumarol patients)
• Avoid concomitant use or adjust XTANDI dose with strong CYP2C8 or inducers
• Safety not established in patients with clinically significant cardiovascular disease
• 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 renal disease

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.

or to speak with a medical expert, please contact:

Marlo Taylor
energi PR
416-425-9143 ext. 11
[email protected]