Lupin's generic enzalutamide tablets have received tentative approval from FDA at doses of 40 mg, 80 mg, 120 mg, and 160 mg via an abbreviated new drug application (ANDA).¹
The tentative approval indicates that the FDA has found the application to meet all required quality, safety, and efficacy standards, but final marketing authorization cannot be granted until relevant patent or exclusivity protections on the reference listed drug (RLD) expire.
The 40 mg and 80 mg formulations were reviewed as bioequivalent to the RLD, enzalutamide (Xtandi), which is currently approved for the treatment of metastatic castration-resistant and castration-sensitive prostate cancer.¹ Notably, the application also includes 120 mg and 160 mg tablet strengths not currently available in the branded formulation, which may offer prescribers and patients additional dosing flexibility if and when the product reaches the market.
Three Things to Know About Generic Enzalutamide
- The FDA has granted tentative approval — not final marketing authorization — to Lupin's generic enzalutamide tablets, meaning commercial launch remains contingent on the resolution of applicable patent or exclusivity protections on the branded RLD, Xtandi.
- Lupin's ANDA includes 40 mg and 80 mg strengths confirmed as bioequivalent to the Astellas reference product, as well as novel 120 mg and 160 mg tablet configurations not currently available in the branded formulation.
- Tentative approval indicates the FDA has determined that Lupin's application meets all quality, safety, and bioequivalence standards required for eventual generic approval of enzalutamide tablets.
What are the current indications for enzalutamide, and which data supported the ANDA for the generic agent?
Enzalutamide was originally approved by the FDA in August 2012 for metastatic castration-resistant prostate cancer (mCRPC) following progression on docetaxel, based on results from the phase 3 AFFIRM trial (NCT00974311).² Subsequent approvals expanded its use to pre-chemotherapy mCRPC and, later, to metastatic castration-sensitive prostate cancer (mCSPC) based on data from the phase 3 ARCHES (NCT02677896) and PREVAIL (NCT01212991) trials.
In November 2023, the FDA approved enzalutamide for non-metastatic CSPC with biochemical recurrence at high risk for metastasis based on data from the phase 3 EMBARK trial (NCT02319837).3 In the primary analysis of EMBARK, enzalutamide plus leuprolide produced significantly longer metastasis-free survival (MFS) compared with leuprolide alone. The median MFS was not reached for either arm (HR, 0.42; 95% CI, 0.30-0.61; P < .0001). Of note, a statistically significant improvement in MFS was also demonstrated for enzalutamide monotherapy vs placebo plus leuprolide (HR, 0.63; 95% CI, 0.46-0.87; P = .0049). In the final OS analysis, the 8-year OS rates were 78.9% (95% CI, 73.9%–83.1%) with enzalutamide plus leuprolide vs 69.5% (95% CI, 64.0%–74.3%) with leuprolide alone (HR, 0.60; 95% CI, 0.44-0.80; P <.001).
The ANDA submission referenced enzalutamide's approved labeling, which encompasses indications studied in pivotal trials, including the phase 3 PREVAIL trial (NCT01212991) in metastatic castration-sensitive prostate cancer and AFFIRM.2
What is the safety profile?
The safety profile of enzalutamide is characterized across 8 randomized controlled trials, in which patients received enzalutamide 160 mg (n = 5110) or placebo (n = 2829) or bicalutamide 50 mg (n = 387) orally once daily.³ In these eight trials, the median duration of treatment was 22.1 months (range, <0.1 to 95.0) with enzalutamide. In the five placebo-controlled trials (AFFIRM, PROSPER, PREVAIL, ARCHES, and EMBARK), the most common adverse effects (≥10%) occurring more frequently (≥2% over placebo) with enzalutamide were musculoskeletal pain, fatigue, hot flush, constipation, decreased appetite, diarrhea, hypertension, hemorrhage, fall, fracture, and headache.2
The prescribing information carries warnings and precautions for seizure—occurring in 0.4% of patients overall and in 2.2% of patients with predisposing factors, as well as for posterior reversible encephalopathy syndrome. Additional labeled warnings include falls and fractures, hypersensitivity reactions, ischemic heart disease, and embryo-fetal toxicity.
In the final OS analysis of EMBARK, no new safety signals emerged with enzalutamide.4 Any-grade treatment-related AEs (TRAEs) were reported in 87.0% of patients in the combination arm vs 89.3% in the enzalutamide monotherapy arm. Serious TRAEs were seen in 8.5% vs 7.6% of patients in these respective arms.
References
- Lupin receives tentative approval from U.S. FDA for enzalutamide tablets. News release. Lupin Limited. June 26, 2026. Accessed June 26, 2026. https://www.lupin.com/media/press-releases/lupin-receives-tentative-approval-from-u-s-fda-for-enzalutamide-tablets
- Enzalutamide (Xtandi) prescribing information. Astellas Pharma US, Inc; 2025. Accessed June 26, 2026. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/213674s011,203415s023lbl.pdf
- FDA approves enzalutamide for non-metastatic castration-sensitive prostate cancer with biochemical recurrence. FDA. November 16, 2023. Accessed June 26, 2026. https://tinyurl.com/5duaj5auLupin 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
- 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
