On August 11, 2023, the U.S. Food and Drug Administration (FDA) approved the fixed dose combination of niraparib and abiraterone acetate (Akeega) plus prednisone for adult patients with deleterious or suspected deleterious BRCA variant (BRCAm) metastatic castration-resistant prostate cancer (mCRPC), as determined by an FDA-approved test.

FDA Approves Niraparib and Abiraterone Acetate Plus Prednisone for BRCA-Variant Metastatic Castration-Resistant Prostate Cancer

Efficacy was evaluated in cohort 1 of MAGNITUDE (NCT03748641), a randomized, double-blind, placebo-controlled trial enrolling 423 patients with homologous recombination repair (HRR) gene-variant mCRPC. Patients were randomized 1:1 to receive niraparib 200 mg and abiraterone acetate 1,000 mg plus prednisone 10 mg daily or placebo and abiraterone acetate plus prednisone daily. Patients were required to have a prior orchiectomy or be receiving gonadotropin-releasing hormone analogues. Patients with mCRPC were eligible if they had not received prior systemic therapy in the mCRPC setting except for less than four months of prior abiraterone acetate plus prednisone and ongoing androgen deprivation therapy. Patients could have received prior docetaxel or androgen receptor targeted therapies in earlier disease settings. Randomization was stratified by prior docetaxel, prior androgen receptor targeted therapy, prior abiraterone acetate plus prednisone, and BRCA status. Of the 423 patients enrolled, 225 (53%) had prospectively determined BRCA gene variations. No benefit was observed in mCRPC patients without an HRR gene variation (cohort 2 of MAGNITUDE) as the criterion for futility was met.

The major efficacy outcome measure was radiographic progression-free survival (rPFS) per RECIST version 1.1 for soft tissue and prostate cancer working group 3 criteria for bone, assessed by blinded independent central review. Overall survival (OS) was an additional endpoint.

A statistically significant improvement in rPFS for niraparib and abiraterone acetate plus prednisone compared to placebo and abiraterone acetate plus prednisone was observed in BRCAm patients with a median of 16.6 months versus 10.9 months (HR 0.53; 95% CI = 0.36, 0.79; p = 0.0014). An exploratory OS analysis in the BRCAm patients demonstrated a median of 30.4 versus 28.6 months (HR 0.79; 95% CI = 0.55, 1.12) favoring the investigational arm. Although a statistically significant improvement in rPFS was seen in the overall cohort 1 intention-to-treat HRR gene variant population (HR 0.73; 95% CI = 0.56, 0.96; p = 0.0217), in the subgroup of 198 (47%) patients with non-BRCA HRR variants, the rPFS hazard ratio was 0.99 (95% CI = 0.67, 1.44) and the OS hazard ratio was 1.13 (95% CI = 0.77, 1.64), indicating that the improvement in the intention-to-treat HRR gene-variant population was primarily attributed to the results seen in the subgroup of patients with BRCAm.

The most common adverse reactions reported in at least 20% of patients treated with niraparib and abiraterone acetate plus prednisone, including laboratory abnormalities, were musculoskeletal pain, fatigue, constipation, hypertension, nausea, decreased hemoglobin, decreased lymphocytes, decreased white blood cells, decreased platelets, decreased neutrophils, increased alkaline phosphatase, increased creatinine, increased potassium, decreased potassium, and increased AST. Among all patients with mCRPC treated with niraparib and abiraterone acetate plus prednisone in cohort 1 of MAGNITUDE (n = 423), 27% required a blood transfusion, including 11% who required multiple transfusions.

The recommended dose is 200 mg niraparib and 1,000 mg abiraterone acetate taken orally once daily in combination with 10 mg of prednisone daily until patients experience disease progression or unacceptable toxicity. Patients receiving niraparib and abiraterone acetate plus prednisone should also receive a concurrent gonadotropin-releasing hormone analogue or should have had bilateral orchiectomy.

View the full prescribing information for niraparib and abiraterone acetate plus prednisone.

The review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.

The application was granted priority review. FDA expedited programs are described in the Guidance for Industry: Expedited Programs for Serious Conditions—Drugs and Biologics

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 800-FDA-1088.

For assistance with single-patient investigational new drug applications, contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.