FDA Approves Xtandi (enzalutamide) for Earlier Stage Prostate Cancer Treatment

The U.S. Food and Drug Administration (FDA) has approved a supplemental New Drug Application for  Xtandi, (enzalutamide), marking a significant advancement in the treatment of prostate cancer. This approval, announced by Astellas Pharma Inc. and Pfizer Inc., comes after the FDA's expedited review and development programs, which included Priority Review and Fast Track designations.

Xtandi, an androgen receptor signaling inhibitor, is now the first and only drug of its kind approved for patients with nonmetastatic castration-sensitive prostate cancer (nmCSPC) who show signs of high-risk biochemical recurrence (BCR). This new approval allows Xtandi, to be used with or without gonadotropin-releasing hormone (GnRH) analog therapy.

Courtney Bugler, President and CEO of ZERO Prostate Cancer, expressed that this approval brings hope to patients:  

"For patients who were previously treated for prostate cancer and had achieved remission, only to later receive the distressing news of disease recurrence with a risk of metastasis, the emotional toll can be profound. This approval of XTANDI is a promising treatment option for the community, offering a ray of hope to patients and their caregivers during these challenging times."   

The approval is grounded in the results of the Phase 3 EMBARK trial,  a comprehensive, randomized, double-blind, placebo-controlled study, in prostate cancer treatment. The trial, presented at the 2023 American Urological Association Annual Meeting and published in the New England Journal of Medicine, evaluated Xtandi in various combinations and as a single agent. The trial demonstrated a significant reduction in the risk of metastasis or death for patients treated with Xtandi, meeting its primary endpoint of metastasis-free survival.

Dr. Neal Shore, a leading prostate cancer specialist and Primary Investigator for the EMBARK trial, emphasized the importance of this development.

"Previously, treatment options for these BCR patients, especially those who have a high likelihood of developing metastases were limited. The FDA approval of Xtandi for patients with nmCSPC with BCR at high risk of metastasis represents an important advancement whereby an androgen deprivation signaling inhibitor, enzalutamide, has achieved standard of care discussion for patient-physician decision-making."  

Similarly, Chris Boshoff, M.D., Ph.D., Executive Vice President at Pfizer, noted the approval as a milestone in Xtandi's legacy, which has shown overall survival benefits in various stages of prostate cancer. This expansion into an earlier disease setting is expected to benefit a larger patient population.

XTANDI is also under review by other global regulatory authorities, including the European Medicines Agency, for an expanded indication in nmCSPC with high-risk BCR, based on the EMBARK trial outcomes.

The EMBARK trial

The EMBARK trial, involving 1,068 patients with high-risk nonmetastatic hormone-sensitive prostate cancer, demonstrated significant results. Enzalutamide combined with leuprolide (355 patients) and enzalutamide as a single agent (355 patients) significantly reduced the risk of metastasis or death compared to placebo plus leuprolide (358 patients). However, adverse events of Grade 3 or higher were reported in 46% of patients in the enzalutamide plus leuprolide group, 50% in the single-agent group, and 43% in the placebo group, leading to treatment discontinuation in 21%, 18%, and 10% of patients respectively.