On 11 August 2023, the US Food and Drug Administration (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 castration-resistant prostate cancer (mCRPC), as determined by an FDA-approved test.

Full prescribing information for Akeega is available here.

Efficacy was evaluated in Cohort 1 of MAGNITUDE (NCT03748641), a randomised, double-blind, placebo-controlled study enroling 423 patients with homologous recombination repair (HRR) gene-mutated mCRPC. Patients were randomised (1:1) to receive niraparib 200 mg and abiraterone acetate 1000 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 (GnRH) analogues. Patients with mCRPC were eligible if they had not received prior systemic therapy in the mCRPC setting except for a short duration of prior abiraterone acetate plus prednisone (up to four months) and ongoing androgen deprivation therapy. Patients could have received prior docetaxel or androgen receptor (AR) targeted therapies in earlier disease settings. Randomisation was stratified by prior docetaxel, prior AR targeted therapy, prior abiraterone acetate plus prednisone, and BRCA status. Of the 423 patients enroled, 225 (53%) had prospectively determined BRCA gene mutations. No benefit was observed in mCRPC patients without an HRR gene mutation (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 patients with BRCA mutation with a median of 16.6 months versus 10.9 months (hazard ratio [HR] 0.53, 95% confidence interval [CI] 0.36, 0.79; p = 0.0014). An exploratory OS analysis in the patients with BRCA mutation demonstrated a median of 30.4 versus 28.6 months (HR 0.79, 95% CI 0.55, 1.12) favouring the investigational arm. While a statistically significant improvement in rPFS was seen in the overall Cohort 1 intention to treat (ITT) HRR population (HR 0.73, 95% CI 0.56, 0.96; p = 0.0217), in the subgroup of 198 (47%) patients with non-BRCA HRR mutations, the HR for rPFS was 0.99 (95% CI 0.67, 1.44) and the HR for OS was 1.13 (95% CI 0.77, 1.64), indicating that the improvement in the ITT HRR gene-mutated population was primarily attributed to the results seen in the subgroup of patients with BRCA mutations.

The most common adverse reactions (≥20%), including laboratory abnormalities, were decreased haemoglobin, decreased lymphocytes, decreased white blood cells, musculoskeletal pain, fatigue, decreased platelets, increased alkaline phosphatase, constipation, hypertension, nausea, decreased neutrophils, 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 Akeega dose is 200 mg niraparib and 1000 mg abiraterone acetate taken orally once daily in combination with 10 mg of prednisone daily until disease progression or unacceptable toxicity. Patients receiving niraparib and abiraterone acetate plus prednisone should also receive a GnRH analogue concurrently or should have had bilateral orchiectomy.

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

This application was granted priority review.

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.

For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact FDA’s Oncology Center of Excellence Project Facilitate.