First and Only Oral Treatment FDA-Approved for Both Non-Metastatic and Metastatic CRPC

TOKYO, Japan and NEW YORK, NY, USA I July 13, 2018 I Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., “Astellas”) and Pfizer Inc. (NYSE: PFE) today announced the U.S. Food and Drug Administration (FDA) approved a supplemental New Drug Application (sNDA) for XTANDI® (enzalutamide), following FDA Priority Review designation, based on results from the Phase 3 PROSPER trial. The FDA action broadens the indication for XTANDI to men with castration-resistant prostate cancer (CRPC), now including men with non-metastatic CRPC. This approval makes XTANDI the first and only oral medication FDA-approved for both non-metastatic and metastatic CRPC. XTANDI was first approved by the FDA in 2012 for the treatment of patients with metastatic CRPC who had previously received docetaxel, and was granted approval in 2014 for chemotherapy-naïve men with metastatic CRPC.

“With today’s approval, there is now a new option for men with non-metastatic CRPC, who are in between the failure of androgen deprivation therapy resulting in CRPC and the onset of metastatic disease,” said Jonathan Simons, M.D., Prostate Cancer Foundation President and CEO. “As a foundation that drives research aimed at improving patient outcomes, it is exciting to see approvals like this, which are vital to help address unmet patient needs.” 

The updated label is based on results from the Phase 3 PROSPER trial, which demonstrated that the use of XTANDI plus androgen deprivation therapy (ADT) significantly reduced the risk of developing metastasis or death compared to ADT alone in men with non-metastatic CRPC. The median for the primary endpoint, metastasis-free survival (MFS), was 36.6 months for men who received XTANDI plus ADT compared to 14.7 months with ADT alone (N=1401; HR=0.29 [95% CI: 0.24-0.35]; p<0.0001). The most common adverse reactions (greater than or equal to 10%) that occurred more frequently (greater than or equal to 2% over placebo) in XTANDI plus ADT-treated patients were: asthenic conditions (40% vs 20%), hot flush (13% vs 7.7%), hypertension (12% vs 5.2%), dizziness (12% vs 5.2%), nausea (11% vs 8.6%) and fall (11% vs 4.1%). Grade 3 or higher adverse reactions were reported in 31 percent of men treated with XTANDI plus ADT and in 23 percent of men treated with ADT alone. Data from the PROSPER study were presented at the 2018 Genitourinary Cancers Symposium (ASCO GU) in February and published in the New England Journal of Medicine in June.

“Reducing the risk of disease progression is an important treatment goal in castration-resistant prostate cancer, since the disease becomes harder to treat as it advances,” said Andy Schmeltz, global president, Oncology, Pfizer. “With XTANDI, men with CRPC now have a clinically proven treatment option that reduces the risk of metastasis. This approval delivers on the potential for XTANDI to help men at an earlier stage of the disease, and we are continuing to evaluate the medicine in an extensive development program across additional prostate cancer populations.” 

“This approval is important progress for men with CRPC, who now have XTANDI as a treatment option regardless of whether or not they have detectable metastatic disease,” said Steven Benner, M.D., senior vice president and global therapeutic area head, Oncology Development, Astellas. “XTANDI is a standard of care in the treatment of men with metastatic CRPC and has been prescribed to more than 250,000 men worldwide since its initial approval in 2012. The expanded indication based on the PROSPER data builds on the body of evidence for XTANDI.”

Pfizer and Astellas are committed to helping patients access XTANDI by providing them with access and reimbursement support resources regardless of their situation. Patients can visit www.XTANDI.com or call 1-855-898-2634 to learn more.

PROSPER Trial Results

The Phase 3 PROSPER trial enrolled 1,401 patients with non-metastatic CRPC. Patients were randomized 2:1 and received either XTANDI plus ADT or placebo plus ADT (ADT alone). Data in the updated XTANDI label demonstrates that the use of XTANDI plus ADT significantly reduced the risk of developing metastases or death compared to ADT alone. The median for the primary endpoint, MFS, was 36.6 months for men who received XTANDI compared to 14.7 months with ADT alone (HR=0.29 [95% CI: 0.24-0.35]; p<0.0001).

The primary efficacy outcome was supported by a statistically significant delay in the time to first use of new antineoplastic therapy (TTA) for patients who received XTANDI plus ADT compared to those who received ADT alone (median 39.6 months vs 17.7 months; HR=0.21 [95% CI: 0.17-0.26]; p < 0.0001). Overall survival (OS) data were not mature at the time of final MFS analysis.

The most common adverse reactions (greater than or equal to 10%) that occurred more frequently (greater than or equal to 2% over placebo) in XTANDI plus ADT-treated patients compared to the ADT alone patients were: asthenic conditions (40% vs 20%), hot flush (13% vs 7.7%), hypertension (12% vs 5.2%), dizziness (12% vs 5.2%), nausea (11% vs 8.6%) and fall (11% vs 4.1%). Grade 3 or higher adverse reactions were reported in 31 percent of men treated with XTANDI plus ADT and in 23 percent of men treated with ADT alone. In the study, 3.4 percent of patients in the XTANDI plus ADT arm and 0.6 percent in the ADT alone arm died from adverse events. Discontinuations with an adverse event as the primary reason were reported for 9.4 percent of patients treated with XTANDI plus ADT vs 6 percent treated with ADT alone.

About Prostate Cancer

Prostate cancer is the second most common cancer in men worldwide.1 More than 164,000 men in the United States are estimated to be newly diagnosed with prostate cancer in 2018.2 In the European Union, the estimated number of new prostate cancer cases in 2015 was 365,000.3

Castration-resistant prostate cancer (CRPC) refers to the subset of men whose prostate cancer progresses despite castrate levels of testosterone (i.e., less than 50 ng/dL).4 Non-metastatic CRPC means there is no clinically detectable evidence of the cancer spreading to other parts of the body (metastases), and there is a rising prostate-specific antigen (PSA) level.5 Many men with non-metastatic CRPC and a rapidly rising PSA level go on to develop metastatic CRPC.6

About XTANDI® (enzalutamide) capsules

XTANDI (enzalutamide) is an androgen receptor inhibitor indicated for the treatment of patients with castration-resistant prostate cancer.

About the Enzalutamide Development Program

Pfizer and Astellas are collaborating on a comprehensive development program that includes studies of enzalutamide across the full spectrum of advanced prostate cancer. 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.

About Astellas

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. For more information, please visit our website at https://www.astellas.com/en.

About Pfizer Oncology

Pfizer Oncology is committed to pursuing innovative treatments that have a meaningful impact on people living with cancer. Our growing pipeline of biologics, small molecules, and immunotherapies is focused on identifying and translating the best scientific breakthroughs into clinical application for patients across a diverse array of solid tumors and hematologic cancers. Today, we have 10 approved oncology medicines and 14 assets currently in clinical development. By maximizing our internal scientific resources and collaborating with other companies, government and academic institutions, as well as patients and non-profit and professional organizations, we are bringing together the brightest and most enterprising minds to take on the toughest cancers. Together we can accelerate breakthrough treatments to patients around the world and work to redefine life with cancer.

About the Pfizer/Astellas Collaboration

In October 2009, Medivation, Inc., which is now part of Pfizer (NYSE:PFE), and Astellas (TSE: 4503) entered into a global agreement to jointly develop and commercialize enzalutamide. 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.

1 American Cancer Society. Global Cancer Facts and Figures (2015). https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/global-cancer-facts-and-figures/global-cancer-facts-and-figures-3rd-edition.pdf. Accessed 01-11-2018.

2 American Cancer Society. Key Statistics for Prostate Cancer. https://www.cancer.org/cancer/prostate-cancer/about/key-statistics.html. Accessed 01-08-2018.

3 European Commission. Epidemiology of prostate cancer in Europe (03-17-2017). https://ec.europa.eu/jrc/en/publication/epidemiology-prostate-cancer-europe. Accessed 01-19-2018.

4 Kirby M, Hirst C, Crawford ED. Characterising the castration-resistant prostate cancer population: a systematic review. Int J Clin Pract 2011;65(11):1180-92.

5 Luo J, Beer T, Graff J. Treatment of nonmetastatic castration-resistant prostate cancer. Oncology 2016;30(4):336-44.

6 Smith MR, Kabbinavar F, Saad F, et al. Natural history of rising serum prostate-specific antigen in men with castrate nonmetastatic prostate cancer. J Clin Oncol 2005;23(13):2918-25.

SOURCE: Astellas Pharma