Phase 3 Study Shows XTANDI® (enzalutamide) plus Leuprolide Significantly Improves Metastasis-Free Survival in Men with Nonmetastatic Prostate Cancer Français
Pfizer and Astellas announce positive top-line results from Phase 3 EMBARK trial
MARKHAM, ON, March 23, 2023 /CNW/ - Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., "Astellas"), the parent company of Astellas Pharma Canada, Inc., has announced positive topline results from the Phase 3 EMBARK trial evaluating XTANDI® (enzalutamide) in men with non-metastatic hormone-sensitive prostate cancer (nmHSPC; also known as non-metastatic castration-sensitive prostate cancer or nmCSPC) with high-risk biochemical recurrence (BCR). Patients enrolled in the trial were randomized to one of three study arms: XTANDI plus leuprolide, placebo plus leuprolide, or XTANDI monotherapy. The study met its primary endpoint with a statistically significant and clinically meaningful improvement in metastasis-free survival (MFS) for patients treated with XTANDI plus leuprolide versus placebo plus leuprolide.
At the time of the analysis, a positive trend in the key secondary endpoint of overall survival (OS) was also observed, but these data were not yet mature. Patients in the trial will be followed for a subsequent final OS analysis. The study also met a key secondary endpoint with a statistically significant and clinically meaningful improvement in MFS for patients treated with XTANDI monotherapy versus placebo plus leuprolide. Additional key secondary endpoints reached statistical significance, including time to PSA progression and time to first use of new antineoplastic therapy. Other secondary endpoints are being analyzed. No new safety signals have been observed to date in the preliminary safety analysis, which is consistent with the established safety profile of XTANDI.
"While current treatment options for localized prostate cancer are intended to be curative, some men remain at higher risk for biochemical recurrence following primary treatment, which may result in metastases," said Ahsan Arozullah, M.D., MPH, Senior Vice President and Head of Development Therapeutic Areas, Astellas. "The EMBARK trial is the first study to demonstrate a statistically significant improvement in MFS using the combination of XTANDI plus leuprolide in men with this stage of disease."
"The topline findings from EMBARK are highly encouraging and we look forward to engaging with health authorities to potentially bring XTANDI to men with non-metastatic hormone sensitive prostate cancer and high-risk biochemical recurrence." said Chris Boshoff, M.D., Ph.D., Chief Development Officer, Oncology and Rare Disease, Pfizer Global Product Development.
Detailed results from EMBARK will be presented at a future medical meeting. These data will also be discussed with regulatory authorities, including Health Canada, to support a potential regulatory submission for XTANDI in this indication.
The Phase 3, randomized, double-blind, placebo-controlled, multi-national trial enrolled 1,068 patients with non-metastatic hormone-sensitive prostate cancer (nmHSPC; also known as non-metastatic castration-sensitive prostate cancer or nmCSPC) and high-risk biochemical recurrence (BCR) at sites in the United States, Canada, Europe, South America, and the Asia-Pacific region. Patients who were considered high-risk BCR had a prostate-specific antigen (PSA) doubling time ≤ 9 months, serum testosterone ≥ 150 ng/dL (5.2 nmol/L), and screening PSA by the central laboratory ≥ 1 ng/mL if they had a radical prostatectomy (with or without radiotherapy) as primary treatment for prostate cancer or at least 2 ng/mL above the nadir if they had radiotherapy only as primary treatment for prostate cancer. Patients in the EMBARK trial were randomized to receive enzalutamide 160 mg daily plus leuprolide, enzalutamide 160 mg as a monotherapy, or placebo plus leuprolide.
The primary endpoint of the trial was metastasis-free survival (MFS) for enzalutamide plus leuprolide and placebo plus leuprolide. MFS is defined as the duration of time in months between randomization and the earliest objective evidence of radiographic progression by central imaging or death. For more information on the EMBARK (NCT02319837) trial go to www.clinicaltrials.gov.
XTANDI has not been approved for the treatment of patients with nmHSPC and high-risk BCR.
Non-metastatic hormone- (or castration-) sensitive prostate cancer (nmHSPC or nmCSPC) means there is no clinically detectable evidence of the cancer spreading to other parts of the body (metastases) and the cancer still responds to medical or surgical treatment to lower testosterone levels.1,2 Of men who have undergone definitive prostate cancer treatment, including radical prostatectomy, radiotherapy, or both, an estimated 20-40% will experience a biochemical recurrence (BCR) within 10 years.3 About 9 out of 10 men with high-risk BCR will develop metastatic disease, and 1 in 3 will die as a result of the recurrence.3 The EMBARK trial focused on men with high-risk BCR. Per the EMBARK protocol, patients with nmHSPC and high-risk BCR are those initially treated by radical prostatectomy or radiotherapy, or both, with a PSA doubling time ≤ 9 months. High-risk BCR patients with a PSA doubling time of ≤ 9 months have a higher risk of metastases and death.4
XTANDI (enzalutamide) is an androgen receptor signaling inhibitor. The recommended dosage of XTANDI is 160 mg (capsules) administered orally once daily with or without food. XTANDI is a standard of care that has received regulatory approvals for use in men with mCSPC, mCRPC, and nmCRPC in Canada and for one or more of these indications in more than 100 countries, including the United States, the European Union and Japan. More than 720,000 patients have been treated with XTANDI globally.5
For more product information, please refer to the XTANDI product monograph.
Astellas Pharma Inc. is a pharmaceutical company conducting business in more than 70 countries around the world. We are promoting the Focus Area Approach that is designed to identify opportunities for the continuous creation of new drugs to address diseases with high unmet medical needs by focusing on Biology and Modality. Furthermore, we are also looking beyond our foundational Rx focus to create Rx+® healthcare solutions that combine our expertise and knowledge with cutting-edge technology in different fields of external partners. Through these efforts, Astellas stands on the forefront of healthcare change to turn innovative science into VALUE for patients. For more information, please visit our website at https://www.astellas.com/en.
Astellas Pharma Canada, Inc. is a Canadian affiliate of Tokyo-based Astellas Pharma Inc. For more information about the Canadian affiliate, please visit our website at https://www.astellas.com/ca/en/.
In October 2009, Medivation, Inc., which is now part of Pfizer (NYSE:PFE), and Astellas (TSE: 4503) entered into a commercial agreement to jointly develop and commercialize XTANDI® (enzalutamide) in the United States, while Astellas has responsibility for manufacturing and all additional regulatory filings globally, as well as commercializing the product outside the United States. Pfizer receives alliance revenues as a share of U.S. profits and receives royalties on sales outside the U.S.
Astellas Forward-Looking Statement
In this press release, statements made with respect to current plans, estimates, strategies and beliefs and other statements that are not historical facts are forward-looking statements about the future performance of Astellas. These statements are based on management's current assumptions and beliefs in light of the information currently available to it and involve known and unknown risks and uncertainties. A number of factors could cause actual results to differ materially from those discussed in the forward-looking statements. Such factors include, but are not limited to: (i) changes in general economic conditions and in laws and regulations, relating to pharmaceutical markets, (ii) currency exchange rate fluctuations, (iii) delays in new product launches, (iv) the inability of Astellas to market existing and new products effectively, (v) the inability of Astellas to continue to effectively research and develop products accepted by customers in highly competitive markets, and (vi) infringements of Astellas' intellectual property rights by third parties.
Information about pharmaceutical products (including products currently in development), which is included in this press release is not intended to constitute an advertisement or medical advice.
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1 Cancer.net. Prostate Cancer: Types of Treatment (12-2022). https://www.cancer.net/cancer-types/prostate-cancer/types-treatment. Accessed March 16, 2023. |
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2 American Society of Clinical Oncology. ASCO Answers: Prostate Cancer (2021). http://www.cancer.net/sites/cancer.net/files/asco_answers_guide_prostate.pdf. Accessed March 16, 2023. |
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3 Ward JF, Moul JW. Rising prostate-specific antigen after primary prostate cancer therapy. Nat Clin Pract Urol. 2005 Apr;2(4):174-82. doi: 10.1038/ncpuro0145. PMID: 16474760. |
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4 Paller, Channing J et al. "Management of patients with biochemical recurrence after local therapy for prostate cancer." Hematology/oncology clinics of North America vol. 27,6 (2013): 1205-19, viii. doi:10.1016/j.hoc.2013.08.005 |
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5 Data on file. Northbrook, IL: Astellas Inc. |
SOURCE Astellas Pharma Canada Inc.
For Media: Marlo Taylor, 647-233-7636, [email protected]
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