Generic Enzalutamide Receives Tentative FDA Approval in Prostate Cancer

The FDA has approved an abbreviated new drug application (ANDA) for enzalutamide (Xtandi) tablets at 40 mg, 80 mg, 120 mg, and 160 mg, according to a press release from the developer, Lupin Limited.¹ Tentative approval indicates that the product has met the FDA's standards for quality, safety, and efficacy, although the generic cannot be commercially launched in the US until any existing patents or regulatory exclusivity on the reference listed drug expire.

The FDA has tentatively approved Lupin's enzalutamide tablets in the 40-mg and 80-mg doses as bioequivalent to Astellas' reference listed drug Xtandi tablets for the indications in the approved labeling. While Xtandi is currently marketed in 40-mg and 80-mg doses, Lupin's proposed 120-mg and 160-mg tablet strengths are intended to provide healthcare professionals and patients with alternative dosing configurations.

Enzalutamide is an androgen receptor signaling inhibitor currently approved by the FDA across multiple prostate cancer indications. In November 2023, the FDA approved enzalutamide for non-metastatic castration-sensitive prostate cancer (CSPC) with biochemical recurrence at high risk for metastasis.² The recommended dose was 160 mg orally daily until disease progression or unacceptable toxicity.

That approval was based on data from the phase 3 EMBARK trial (NCT02319837), which enrolled 1068 patients with non-metastatic CSPC and high-risk biochemical recurrence defined by a prostate-specific antigen (PSA) doubling time of 9 months or fewer. Patients were randomly assigned to enzalutamide plus leuprolide, leuprolide alone, or enzalutamide monotherapy.

The primary analysis of EMBARK demonstrated significantly longer metastasis-free survival (MFS) with enzalutamide plus leuprolide compared with leuprolide alone. The final overall survival (OS) analysis of the trial was published in the New England Journal of Medicine.³ The 8-year OS rate was 78.9% (95% CI, 73.9%–83.1%) with enzalutamide plus leuprolide vs 69.5% (95% CI, 64.0%–74.3%) with leuprolide alone, representing a 40% reduction in the risk of death (HR, 0.60; 95% CI, 0.44-0.80; P <.001). Enzalutamide monotherapy, with an 8-year OS rate of 73.1% (95% CI, 67.6%-77.9%) did not demonstrate a statistically significant OS benefit vs leuprolide alone (HR, 0.83; 95% CI, 0.63-1.10; P = .19), though it has retained a role for patients prioritizing preservation of sexual health, supported by patient-reported outcome analyses from the trial.

The primary end point of the trial was MFS. OS was an alpha-controlled key secondary end point. Prespecified secondary end points included time to first use of new antineoplastic therapy and the time to first symptomatic skeletal event, as well as progression-free survival as an exploratory end point.

No new safety signals emerged in the final OS analysis. Any-grade treatment-related AEs (TRAEs) occurred in 87.0% of the combination arm vs 89.3% of the enzalutamide monotherapy arm; of which 19.3% vs 20.3% were related to the study drug. Serious TRAEs occurred in 8.5% vs 7.6% of the respective arms.

The most common AEs occurring in at least 30% of patients across the combination arm were hot flashes (69.7%) and fatigue (43.6%). Breast-related AEs, including gynecomastia (46.0%), nipple pain (15.3%), and breast tenderness (14.4%), were most frequent in the enzalutamide monotherapy group.

“The final analysis of OS in the EMBARK trial shows that, despite prolonged treatment suspension as mandated by the protocol in the case of undetectable PSA at week 36, enzalutamide plus leuprolide resulted in longer OS than leuprolide alone among patients with high-risk biochemical recurrence and no evidence of metastasis on conventional imaging,” Neal D. Shore, MD, FACS, medical director of the Carolina Urologic Research Center and first author of the EMBARK trial, wrote in the publication with study coinvestigators.³

References

1. Lupin receives tentative approval from U.S. FDA for enzalutamide tablets. News release. Lupin Limited. June 26, 2026. Accessed June 26, 2026. https://tinyurl.com/8n4aes2d
2. FDA approves enzalutamide for non-metastatic castration-sensitive prostate cancer with biochemical recurrence. FDA. November 16, 2023. Accessed June 26, 2026. https://tinyurl.com/5duaj5au
3. Shore ND, de Almeida Luz M, De Giorgi U, et al. Improved survival with enzalutamide in biochemically recurrent prostate cancer. N Engl J Med. 2026;394(6):563-575. doi:10.1056/NEJMoa2510310