Medivation and Astellas Announce the Phase 3 PREVAIL Trial of XTANDI▼(TM) (Enzalutamide) Meets Both Co-Primary Endpoints

TOKYO and SAN FRANCISCO, October 22, 2013 /PRNewswire/ --

        
        - Study will be stopped early and enzalutamide offered to all qualified
          study participants
        - 30% Reduction in the Risk of Death, Hazard Ratio = 0.70 (p<0.0001)
        - 81% Reduction in the Risk of Radiographic Progression or Death, Hazard Ratio =
          0.19(p <0.0001)

Astellas Pharma Inc. and Medivation, Inc. today announced that the Independent Data Monitoring Committee (IDMC) has informed the companies of positive results from a planned interim analysis of the Phase 3 PREVAIL trial of XTANDI (enzalutamide) in more than 1,700 men with metastatic castration-resistant prostate cancer (mCRPC) that has progressed despite androgen deprivation therapy and who have not received chemotherapy[i]. Given the observed benefits in the trial's co-primary endpoints of overall survival and radiographic progression-free survival, and considering the observed safety profile, the IDMC concluded enzalutamide demonstrated a favorable benefit-risk ratio. The IDMC recommended the study be stopped and patients treated with placebo be offered enzalutamide. Additional data from the Phase 3 PREVAIL results, including safety data, will be submitted for presentation at an upcoming medical conference.

The IDMC informed the companies of the following results:[i]

        
        - Patients treated with enzalutamide demonstrated a statistically
          significant overall survival advantage compared with patients receiving placebo
          (p<0.0001). Enzalutamide provided a 30% reduction in risk of death compared with
          placebo (Hazard Ratio=0.70; 95% confidence interval (0.59-0.83).
        - Patients treated with enzalutamide demonstrated a statistically significant
          radiographic progression-free survival advantage compared with patients receiving
          placebo (p<0.0001). Enzalutamide provided an 81% reduction in risk of radiographic
          progression or death compared with placebo (Hazard Ratio=0.19); 95% confidence
          interval (0.15-0.23).
        - The percentage of patients alive in the enzalutamide arm was 72% as compared
          with 65% in the placebo arm at the time of the interim analysis data cut-off date.
        - Treatment with enzalutamide resulted in a calculated point estimate for median
          overall survival of 32.4 months (95% confidence interval, 31.5 months-upper limit not
          yet reached) versus 30.2 months (95% confidence interval, 28 months-upper limit not
          yet reached) for patients receiving placebo. Because the trial will be stopped early
          with the majority of patients still alive, the estimated median survivals are not as
          precise as the hazard ratio. The hazard ratio takes into account available information
          about the trial endpoint from all patients whereas the median is a single point
          estimate of a much smaller number of patients at risk.
        - The median radiographic progression-free survival was not yet reached (95%
          confidence intervals 13.8 months-upper limit not yet reached) in the enzalutamide arm
          and was 3.9 months (95% confidence interval, 3.7-5.4 months) in the placebo arm.
        - Given the overall survival benefit and the observed safety profile, the IDMC
          considered the overall benefit-risk ratio to favour the enzalutamide arm and
          recommended unequivocally that patients receiving placebo be offered treatment with
          enzalutamide.

Of the 1,715 patients treated in the blinded PREVAIL study, two patients were reported by investigators to have had a seizure event. The full analysis of the safety data will become available upon final database lock and unblinding.

Enzalutamide is a novel, oral, once-daily androgen receptor (AR) signaling inhibitor that inhibits multiple steps of the AR signaling pathway in three distinct ways: It blocks androgen binding to the androgen receptors, inhibits nuclear translocation of the AR complex and impairs association of the AR complex with DNA, thus impairing tumour cell replication and tumour growth.[ii]

"These are exciting times in the treatment of mCRPC and the discovery and development of enzalutamide represents a significant advance," said Professor Bertrand Tombal, MD, PhD, Chairman of the Division of the Urology, Cliniques Universitaires Saint Luc, Université Catholique de Louvain (UCL) and European Principal Investigator for PREVAIL. "The treatment options available to men with mCRPC have expanded significantly over the last few years, but the bottom line is that more than 70,000 men die each year from the disease. The registration of docetaxel was a major step towards cure but, 10 years later, we must acknowledge that many patients never received docetaxel, as indicated by recent Swedish data. These interim data for enzalutamide show us that its use before docetaxel induces a dramatic improvement in time to disease progression. These results demonstrate significant survival benefit in this setting, which are truly unprecedented and represent an important step forward in making this promising treatment available for men with advanced prostate cancer across Europe, following regulatory approval."

"We are very excited about these results and the potential to offer a new treatment option for patients with metastatic castration resistant prostate cancer, in the pre-chemotherapy setting," said Dr Mike Holmes, Senior Medical Director, Oncology, Astellas Pharma Europe Ltd. "There remains a high unmet patient need for a new treatment that offers patients with advanced prostate cancer, not only the opportunity to live for longer, but to do so with a good quality of life. We are committed to work with our partners, Medivation, to seek the necessary European regulatory approval for this expanded use of enzalutamide, based on the results of PREVAIL."

Medivation and Astellas will initiate meetings with and submission to regulatory agencies in 2014.

Enzalutamide is currently licensed in Europe for the treatment of adult men with metastatic castration-resistant prostate cancer whose disease has progressed on or after docetaxel therapy.[iii]

Notes to Editors:

About PREVAIL

The Phase 3 PREVAIL trial is a randomised, double-blind, placebo-controlled, multi-national trial that enrolled over 1,700 patients at sites in the United States, Canada, Europe, Australia, Russia, Israel and Asian countries, including Japan. The trial enrolled patients with metastatic prostate cancer whose disease progressed despite treatment with androgen deprivation therapy and had not received chemotherapy. The co-primary endpoints of the trial are 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. Targeted enrollment was completed in May 2012 and the interim analysis was pre-specified after approximately 516 death events.[iv]

About XTANDI

XTANDI (enzalutamide) is a novel, oral, once-daily androgen receptor signaling inhibitor which works in three distinct ways: it inhibits testosterone binding to androgen receptors, nuclear translocation of androgen receptors; and DNA binding and activation by androgen receptors. In Europe, enzalutamide is currently licensed for the treatment of adult men with metastatic castration-resistant prostate cancer whose disease has progressed on or after docetaxel therapy.

About Astellas Pharma Europe Ltd

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