Phase 3 PROSPER Trial Shows XTANDI Significantly Reduced the Risk of Metastasis or Death by 71 Percent in Men with Non-Metastatic Castration-Resistant Prostate Cancer

Astellas Pharma Inc. (TSE: 4503, President and CEO: Yoshihiko Hatanaka, “Astellas”) and Pfizer Inc. (NYSE: PFE) announced today results from the Phase 3 PROSPER trial in patients with non-metastatic (M0) Castration-Resistant Prostate Cancer (CRPC).

The results show that the use of XTANDI® (enzalutamide) plus androgen deprivation therapy (ADT) significantly reduced the risk of developing metastases or death by 71 percent compared to ADT alone. The median for the primary endpoint, metastasis-free survival (MFS), was 36.6 months for men who received XTANDI compared to 14.7 months with ADT alone (n=1401; HR=0.29 [95% CI: 0.24-0.35]; p<0.0001). These data will be presented at the 2018 Genitourinary Cancers Symposium in San Francisco.

Marketing applications based on the results of the PROSPER study have been submitted to the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA). The FDA and EMA each have a filing review period during which they evaluate whether an application is complete and acceptable for filing. The data are also being submitted to additional regulatory authorities around the world.

“In patients with non-metastatic CRPC, there is a high unmet need to delay development of metastases and the progression to advanced prostate cancer. There are currently no approved systemic therapies for patients with non-metastatic CRPC in the U.S.,” said Maha Hussain, M.D., Robert H. Lurie Comprehensive Cancer Center of Northwestern University, who will present the data. “In the PROSPER trial, treatment with enzalutamide plus ADT delayed the development of metastases compared to standard of care ADT alone and, if approved, may provide men with non-metastatic CRPC an important new treatment option.”

PROSPER also investigated time to prostate-specific antigen (PSA) progression, time to first use of new antineoplastic therapy and overall survival (OS) as key secondary endpoints. The analysis demonstrated that patients who received XTANDI plus ADT had a 93 percent reduction in relative risk of PSA progression compared to patients who received ADT alone (HR=0.07 [95% CI: 0.05-0.08]; P<0.0001). XTANDI plus ADT delayed the median time to PSA progression by 33.3 months (37.2 months [95% CI: 33.1-NR] versus 3.9 months with ADT alone [95% CI: 3.8-4.0]).

XTANDI plus ADT prolonged the median time to first use of new antineoplastic therapy by 21.9 months versus ADT alone (39.6 months [95% CI: 37.7-NR] vs. 17.7 months [95% CI: 16.2-19.7]), a 79 percent relative risk reduction (HR=0.21 [95% CI: 0.17-0.26]; p<0.0001). At the time of the first interim analysis, median OS had not yet been reached in either treatment arm. However, these interim results demonstrated a trend in favor of XTANDI that was not statistically significant (HR=0.80 [95% CI: 0.58-1.09]; p=0.1519).

Adverse events in the PROSPER trial were generally consistent with those reported in prior enzalutamide clinical trials in patients with metastatic CRPC. Grade 3 or higher adverse events were reported in 31 percent of men treated with XTANDI plus ADT and in 23 percent of men treated with ADT alone. The most common (≥2%) Grade 3 or higher adverse events that were reported more often in XTANDI plus ADT-treated patients included hypertension (5% vs. 2%) and fatigue (3% vs. 1%). Major adverse cardiovascular events were reported in 5 percent of patients who received XTANDI plus ADT and 3 percent with ADT alone. Three seizures (<1%) were reported with XTANDI plus ADT patients and none were reported for those who received ADT alone. The percentage of patients in whom adverse events were the primary reason leading to treatment discontinuation was low in both study arms (9% with XTANDI plus ADT versus 6% with ADT alone).

About PROSPER
The Phase 3 randomized, double-blind, placebo-controlled, multi-national trial enrolled approximately 1,400 patients with non-metastatic castration-resistant prostate cancer (CRPC) at sites in the United States, Canada, Europe, South America and the Asia-Pacific region. PROSPER enrolled patients with prostate cancer that had progressed, based on a rising prostate-specific antigen (PSA) level despite androgen deprivation therapy (ADT), but who had no symptoms and no prior or present evidence of metastatic disease. The trial evaluated enzalutamide at a dose of 160 mg taken orally once daily plus ADT, versus placebo plus ADT.

The primary endpoint of the PROSPER trial, metastasis-free survival (MFS), is a measure of the amount of time that passes until a cancer can be radiographically detected as having metastasized, or until death, within 112 days of treatment discontinuation. Secondary endpoints included time to PSA progression, time to first use of antineoplastic therapy and overall survival.

Astellas Pharma Inc., based in Tokyo, Japan, is a company dedicated to improving the health of people around the world through the provision of innovative and reliable pharmaceutical products. We focus on Urology, Oncology, Immunology, Nephrology and Neuroscience as prioritized therapeutic areas while advancing new therapeutic areas and discovery research leveraging new technologies/modalities. We are also creating new value by combining internal capabilities and external expertise in the medical/healthcare business. Astellas is on the forefront of healthcare change to turn innovative science into value for patients. For more information, please visit our website at www.astellas.com/en.

About Pfizer Oncology
Pfizer Oncology is committed to pursuing innovative treatments that have a meaningful impact on those living with cancer. As a leader in oncology speeding cures and accessible breakthrough medicines to patients, Pfizer Oncology is helping to redefine life with cancer. Our strong pipeline of biologics, small molecules and immunotherapies, one of the most robust in the industry, is studied with precise focus on identifying and translating the best scientific breakthroughs into clinical application for patients across a wide range of cancers. By working collaboratively with academic institutions, individual researchers, cooperative research groups, governments and licensing partners, Pfizer Oncology strives to cure or control cancer with its breakthrough medicines. Because Pfizer Oncology knows that success in oncology is not measured solely by the medicines you manufacture, but rather by the meaningful partnerships you make to have a more positive impact on people’s lives. Learn more about how Pfizer Oncology is applying innovative approaches to improve the outlook for people living with cancer at http://www.pfizer.com/research/therapeutic_areas/oncology.

About the Pfizer/Astellas Collaboration
In October 2009, Medivation, Inc., which is now part of Pfizer , 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 other cancers. Ongoing studies of enzalutamide in prostate cancer include the ARCHES trial in metastatic hormone-sensitive prostate cancer and the EMBARK trial in non-metastatic hormone-sensitive prostate cancer. The companies jointly commercialize XTANDI in the United States and Astellas has responsibility for manufacturing and all additional regulatory filings globally, as well as commercializing XTANDI outside the United States.