FDA approves niraparib and abiraterone acetate plus prednisone for BRCA2-mutated metastatic castration-sensitive prostate cancer

Regulatory approval: On Dec 12, 2025, the FDA approved niraparib plus abiraterone acetate (Akeega) with prednisone for adults with deleterious or suspected deleterious BRCA2-mutated metastatic castration-sensitive prostate cancer, as determined by an FDA-approved test. Approval was supported by AMPLITUDE (NCT04497844), where radiographic PFS improved in the overall HRR-mutated population, with exploratory analyses suggesting the benefit was primarily driven by the BRCA2-mutated subgroup.

FDA approval (Dec 12, 2025)

The FDA approved niraparib plus abiraterone acetate (Akeega) with prednisone for adults with deleterious or suspected deleterious BRCA2-mutated metastatic castration-sensitive prostate cancer (mCSPC), as determined by an FDA-approved test.

Evidence base: AMPLITUDE (NCT04497844)

Approval was supported by AMPLITUDE, a randomized, double-blind trial (N=696) in patients with homologous recombination repair gene–mutated (HRRm) mCSPC. Patients were randomized 1:1 to niraparib + abiraterone acetate plus prednisone (AAP) vs placebo + AAP; all received ongoing androgen deprivation therapy.

  • Primary endpoint: investigator-assessed radiographic PFS (rPFS); OS was also assessed.
  • Overall HRRm population: statistically significant rPFS improvement with niraparib + AAP vs placebo + AAP.
  • Exploratory BRCA2m subgroup (n=323): rPFS HR 0.46 (95% CI 0.32–0.66); median rPFS NE (95% CI 41, NE) vs 26 months (95% CI 18–28) for placebo + AAP.
  • Exploratory non-BRCA2m subgroup (n=373): rPFS HR 0.88 (95% CI 0.63–1.24), suggesting the overall benefit was primarily attributed to BRCA2m results.
  • OS interim (BRCA2m): 91 deaths; 22% (36) on niraparib + AAP vs 34% (55) on placebo + AAP.

Safety, dosing, and review notes

Label warnings/precautions include MDS/AML, myelosuppression, hypokalemia, fluid retention/cardiovascular adverse reactions, hepatotoxicity, adrenocortical insufficiency, hypoglycemia, increased fractures and mortality with radium Ra 223, PRES, and embryo-fetal toxicity. Recommended dosing: niraparib 200 mg + abiraterone acetate 1,000 mg once daily with prednisone 5 mg once daily until progression or unacceptable toxicity; patients should also receive a GnRH analog or have had bilateral orchiectomy. The application received priority review and used an FDA Assessment Aid submission.

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