On December 12, 2025, the U.S. Food and Drug Administration (FDA) granted approval for AKEEGA® (niraparib and abiraterone acetate dual-action tablet) in combination with prednisone for the treatment of adult patients with deleterious or suspected deleterious BRCA2-mutated metastatic castration-sensitive prostate cancer (mCSPC). This supplemental New Drug Application (sNDA) approval marks AKEEGA as the first and only precision medicine combination of a PARP inhibitor and androgen receptor pathway inhibitor specifically indicated for BRCA2-mutated mCSPC, expanding its prior 2023 approval for BRCA-mutated metastatic castration-resistant prostate cancer (mCRPC).
The approval is supported by data from the Phase 3 AMPLITUDE trial (NCT04497844), a randomized, double-blind, placebo-controlled study involving 696 patients with homologous recombination repair (HRR) gene-altered mCSPC across 32 countries. Patients received either niraparib/abiraterone acetate plus prednisone and androgen deprivation therapy (ADT) or placebo/abiraterone acetate plus prednisone and ADT. In an exploratory subgroup analysis of 323 patients with BRCA2 mutations, AKEEGA demonstrated a significant 54% reduction in the risk of radiographic progression-free survival (rPFS) events or death (hazard ratio [HR] 0.46; 95% CI: 0.32–0.66), with median rPFS not estimable in the treatment arm versus 26 months in the control arm. Additionally, time to symptomatic progression was prolonged by 59% (HR 0.41; 95% CI: 0.29–0.65). Exploratory analyses in non-BRCA2 HRR-mutated patients showed no meaningful benefit (HR 0.88), underscoring the targeted efficacy in BRCA2-mutated disease.
Patients with BRCA2 mutations, comprising a subset of the approximately 25% of mCSPC cases with HRR alterations, face more aggressive disease with faster progression and shorter survival compared to those without such mutations. This approval addresses a critical unmet need by offering a biomarker-driven therapy earlier in the disease continuum.
The safety profile in AMPLITUDE was consistent with known effects of the individual agents, with common adverse reactions including anemia, musculoskeletal pain, fatigue, and hypertension. Serious adverse events occurred in 36% of patients, with fatal reactions in 4.9%. Warnings include risks of myelosuppression, hypertension, hepatotoxicity, and embryo-fetal toxicity. This milestone advances personalized treatment options in prostate cancer, supported by Johnson & Johnson’s commitment to innovative therapies across the disease spectrum.
