Astellas Pharma Europe Limited

Medivation and Astellas Announce the Phase 3 PREVAIL Trial of XTANDI?(TM) (Enzalutamide) Meets Both Co-Primary Endpoints of Overall Survival and Radiographic Progression-Free Survival in Chemotherapy-Naïve Patients with Advanced Prostate Cancer

Tokyo And San Francisco (ots/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

Astellas Pharma Europe Ltd., located in the UK, is the European headquarters 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 pharmaceuticals. The organisation's focus is to deliver outstanding R&D and marketing to continue growing in the world pharmaceutical market. Astellas Pharma Europe Ltd. is responsible for 21 affiliate offices located across Europe, the Middle East and Africa, an R&D site and three manufacturing plants. The company employs approximately 4,350 staff across these regions. For more information about Astellas Pharma Europe, please visit http://www.astellas.eu.

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 http://www.astellas.com/en.

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 http://www.medivation.com.

About the Medivation/Astellas Collaboration

In October 2009, Medivation and Astellas entered into a global agreement to jointly develop and commercialise enzalutamide (formerly MDV3100).The companies are collaborating on a comprehensive development programme that includes studies to develop enzalutamide across the full spectrum of advanced prostate cancer. The companies are jointly commercialising enzalutamide in the United States and Astellas will have responsibility for commercialising enzalutamide outside the U.S, pending further regulatory authorisation. To date, enzalutamide has been filed in Japan, Switzerland and Brazil, and has received authorisation in the US, Canada and the EU.

References

i. Data on file: IDMC correspondence

ii. Tran C, Ouk S, Clegg NJ et al. Development of a second-generation antiandrogen for treatment of advanced prostate cancer. Science 2009; 324 (5928): 787-790

iii. European Medicines Agency, Xtandi (enzalutamide) Summary of Product Characteristics, 2013

iv. http://clinicaltrials.gov/ct2/show/NCT01212991. Last accessed 21.10.13

Job number: ENZ/13/0093/EU
Date of preparation: October 2013
 

Contact:

Contact: Mindy Dooa. Astellas Pharma Europe Ltd,
Mindy.Dooa@eu.astellas.com, +44-(0)7826-912339



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