FDA approves niraparib and abiraterone acetate plus prednisone for BRCA-mutated metastatic castration-resistant prostate cancer
Regulatory approval: On Aug 11, 2023, the FDA approved the fixed-dose combination niraparib/abiraterone acetate (Akeega) with prednisone for adults with deleterious or suspected deleterious BRCA-mutated metastatic castration-resistant prostate cancer (mCRPC), as determined by an FDA-approved test. Approval was supported by Cohort 1 of the phase 3 MAGNITUDE trial, where BRCA-mutated patients had improved radiographic PFS versus placebo plus abiraterone/prednisone; OS findings were exploratory.
FDA approval (Aug 11, 2023)
The US FDA approved the fixed-dose combination of niraparib and abiraterone acetate (Akeega; Janssen Biotech, Inc.), with prednisone, for adult patients with deleterious or suspected deleterious BRCA-mutated metastatic castration-resistant prostate cancer (mCRPC), as determined by an FDA-approved test.
Key efficacy evidence
Efficacy was evaluated in Cohort 1 of MAGNITUDE (NCT03748641), a randomized, double-blind, placebo-controlled trial (n=423) enrolling patients with HRR gene–mutated mCRPC. Patients were randomized 1:1 to niraparib 200 mg + abiraterone 1,000 mg + prednisone 10 mg daily vs placebo + abiraterone + prednisone. The primary outcome was radiographic PFS (rPFS) by blinded independent central review (RECIST 1.1/PCWG3); OS was an additional endpoint.
Among patients with BRCA mutations (225/423; 53%), median rPFS was 16.6 vs 10.9 months (HR 0.53; 95% CI 0.36–0.79; p=0.0014). An exploratory OS analysis showed median 30.4 vs 28.6 months (HR 0.79; 95% CI 0.55–1.12).
No benefit was observed in patients without an HRR gene mutation (Cohort 2) per futility criteria.
Safety and dosing (selected)
Common adverse reactions (≥20%), including laboratory abnormalities, included cytopenias (e.g., decreased hemoglobin/platelets/WBC), fatigue, musculoskeletal pain, hypertension, nausea, and creatinine/potassium/AST changes. In Cohort 1, 27% required a blood transfusion (11% multiple). Recommended dose: Akeega 200/1,000 mg once daily + prednisone 10 mg daily, with concurrent GnRH analog or prior bilateral orchiectomy.