Leuprolide Acetate

NEW YORK, NY, USA & TOKYO, Japan I July 10, 2025 I Pfizer Inc. (NYSE: PFE) and Astellas Pharma Inc. (TSE: 4503, President and CEO: Naoki Okamura, “Astellas”) today announced positive topline results from the overall survival (OS) analysis from the Phase 3 EMBARK study evaluating XTANDI ® (enzalutamide), in combination with leuprolide and as a monotherapy, in men with non-metastatic hormone-sensitive prostate cancer (nmHSPC; also known as nonmetastatic castration-sensitive prostate cancer or nmCSPC) with biochemical recurrence (BCR) at high risk for metastasis. For patients treated with XTANDI plus leuprolide versus placebo plus leuprolide, EMBARK met the key secondary endpoint with a statistically significant and clinically meaningful improvement in OS. Results also showed a favorable trend towards improved OS for patients treated with XTANDI monotherapy versus placebo plus leuprolide, however the difference did not reach statistical significance. No new safety signals were observed in the analysis, and the safety results were consistent with the demonstrated safety profile of XTANDI. 1 “These data demonstrate that treatment with XTANDI can extend life for men with nmHSPC and high-risk BCR who have relapsed after initial curative-intent therapy with prostatectomy, radiation therapy or both, further validating EMBARK’s metastasis-free survival (MFS) data,” said Neal Shore, M.D., F.A.C.S, START Carolinas/Carolina Urologic Research Center. “While men with nmHSPC with high-risk BCR now have expanded treatment choices, these results demonstrate a clear clinical benefit, including both MFS and OS, supporting the clinical practice of initiating XTANDI for these patients.” Among men who have undergone definitive prostate cancer treatment, including radical prostatectomy, radiotherapy, or both, an estimated 20-40% will experience BCR within 10 years. 2 About nine out of 10 men with high-risk BCR will develop metastatic disease, and one in three will die as a result of their metastatic prostate cancer. 3 “XTANDI is the only androgen receptor inhibitor-based regimen to demonstrate a survival benefit in metastatic HSPC and nmHSPC with high-risk BCR, as well as castration-resistant prostate cancer, highlighting its significant patient impact in advanced prostate cancer,” said Johanna Bendell, M.D., Oncology Chief Development Officer, Pfizer. “These positive results add to the robust clinical support for the use of XTANDI and broaden clinical confidence, offering men with high-risk BCR evidence that they might live longer when they start XTANDI early.” In the EMBARK study, patients were randomized to one of three study arms: XTANDI plus leuprolide, placebo plus leuprolide, or XTANDI monotherapy. An initial analysis was previously reported in The New England Journal of Medicine in 2023, demonstrating that the study met its primary endpoint with a statistically significant and clinically meaningful improvement in MFS for patients treated with XTANDI plus leuprolide versus placebo plus leuprolide. 4 The most common adverse events (occurring in ≥10% of patients) in the combination group and the leuprolide-alone group were hot flashes and fatigue. The most common adverse events in the monotherapy group were gynecomastia, hot flashes, and fatigue. 4 XTANDI is currently approved in more than 80 countries, including in the United States, European Union, and Japan. “Over 1.5 million men with advanced prostate cancer around the world have benefited from treatment with XTANDI since its initial approval in 2012,” 5 said Shontelle Dodson, Executive Vice President, Head of Medical Affairs, Astellas. “The scope and rigor of the EMBARK trial exemplify Astellas’ and Pfizer’s longstanding commitment to the prostate cancer community, and we look forward to sharing detailed findings in a future scientific forum.” Detailed OS results from EMBARK will be presented at a future medical meeting. About EMBARK 4 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) with 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 monotherapy, or placebo plus leuprolide. The primary results from the EMBARK trial were published in The New England Journal of Medicine in 2023. The primary endpoint of the trial was metastasis-free survival (MFS) for enzalutamide plus leuprolide versus 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 . About Non-Metastatic Hormone-Sensitive Prostate Cancer with High-Risk Biochemical Recurrence Non-metastatic hormone- (or castration-) sensitive prostate cancer (nmHSPC or nmCSPC) means there is no detectable evidence of the cancer spreading to distant parts of the body (metastases) with conventional radiological methods (CT/MRI) and the cancer still responds to medical or surgical treatment to lower testosterone levels. 6,7 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. 8 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. 8 The EMBARK trial focused on men with high-risk BCR. Per the EMBARK protocol, patients with nmHSPC with high-risk BCR are those initially treated by radical prostatectomy or radiotherapy, or both, with a PSA doubling time ≤ 9 months. Patients with nmCSPC who experience BCR after local therapy may be at a higher risk of metastases and death if their PSA doubling time is ≤ 9 months. 9 About XTANDI ® (enzalutamide) XTANDI (enzalutamide) is an androgen receptor signaling inhibitor. XTANDI is a standard of care and has received regulatory approvals in one or more countries around the world for use in men with metastatic hormone-sensitive prostate cancer (mHSPC), metastatic castration-resistant prostate cancer (mCRPC), non-metastatic castration-resistant prostate cancer (nmCRPC) and non-metastatic hormone-sensitive prostate cancer (nmHSPC) with high-risk biochemical recurrence (BCR). XTANDI is currently approved for one or more of these indications in more than 80 countries, including in the United States, European Union and Japan. Over 1.5 million patients have been treated with XTANDI globally. 5 About XTANDI (enzalutamide) and U.S. Important Safety Information XTANDI (enzalutamide) is indicated for the treatment of patients with: Please see Full Prescribing Information for additional safety information. About Astellas 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 at 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 . About Pfizer Oncology At Pfizer Oncology, we are at the forefront of a new era in cancer care. Our industry-leading portfolio and extensive pipeline includes three core mechanisms of action to attack cancer from multiple angles, including small molecules, antibody-drug conjugates (ADCs), and bispecific antibodies, including other immune-oncology biologics. We are focused on delivering transformative therapies in some of the world’s most common cancers, including breast cancer, genitourinary cancer, hematology-oncology, and thoracic cancers, which includes lung cancer. Driven by science, we are committed to accelerating breakthroughs to help people with cancer live better and longer lives. 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 XTANDI (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. SOURCE: Pfizer

In 2023, the drug won FDA approval as a treatment for patients with non-metastatic hormone-sensitive prostate cancer (nmHSPC) at a high risk of biochemical recurrence. Pfizer and Astellas are underlining the benefits of Xtandi as part of a combination therapy for certain patients with non-metastatic hormone-sensitive prostate cancer (nmHSPC) with an overall survival win.The new data come from the companies’ phase 3 Embark study, which in 2023 led to the FDA approval of Xtandi in patients with nmHSPC with biochemical recurrence (BCR) at high risk of metastasis.In the trial, Xtandi was studied as a single agent and in combination with leuprolide against placebo and leuprolide. For the trial's primary endpoint, the Xtandi combo delivered a statistically significant improvement in metastasis-free survival compared with placebo and leuprolide.At the time, the trial's overall survival data were mature.Now, Xtandi plus leuprolide has proved it can, in fact, extend the lives of these patients, demonstrating a “statistically significant and clinically meaningful improvement” in overall survival, Pfizer announced in a July 10 press release.Xtandi as a monotherapy, however, did not reach statistical significance on the overall survival measure.The results solidify the Xtandi regimen as the first and only androgen receptor inhibitor-based treatment to yield an overall survival benefit in the patient group, according to the release.“These positive results add to the robust clinical support for the use of Xtandi and broaden clinical confidence, offering men with high-risk BCR evidence that they might live longer when they start Xtandi early,” Pfizer's oncology chief development officer, Johanna Bendell, M.D., said in a press release.Xtandi was first approved in 2012 for late-stage castration-resistant prostate cancer and has since picked up several expansions, with the latest in 2023 marking its move into earlier prostate cancer treatment settings. An estimated 20% to 40% of men who have been treated for prostate cancer will experience a BCR within 10 years, with about 9 out of 10 men with high-risk BCR developing metastatic disease. Xtandi, a flagship product for Astellas, delivered a significant 21.6% growth spurt during the company's 2024 fiscal year, generating 912 billion yen ($6.2 billion). Sales expanded “in all regions” over the year, the company noted.