Akeega, an Oral Combo Therapy for BRCA-Mutated mCRPC, Gets FDA Approval

The US Food and Drug Administration (FDA) has approved Akeega (niraparib and abiraterone acetate) for the treatment of adults with deleterious or suspected deleterious BRCA-mutated (BRCAm) metastatic castration-resistant prostate cancer (mCRPC), as determined by an FDA-approved test.

Akeega is an oral therapy that combines niraparib, a PARP inhibitor, and abiraterone acetate, a CYP17 inhibitor, into a single tablet. The approval was based on data from the randomized, double-blind, phase 3 MAGNITUDE study (ClinicalTrials.gov Identifier: NCT03748641).

Study participants with homologous recombination repair (HRR) gene-mutated mCRPC (cohort 1) were randomly assigned to receive niraparib at 200 mg and abiraterone at 1000 mg (n=212) or placebo and abiraterone (n=211) until unacceptable toxicity or progression. All patients received prednisone at 10 mg daily and a gonadotropin-releasing hormone analog or had prior bilateral orchiectomy.

In this study population, 53% of patients (n=225) had BRCA mutations. The primary endpoint was radiographic progression free survival (rPFS). Overall survival (OS) was an additional outcome measure.

Findings showed a significant improvement in rPFS with niraparib-abiraterone over placebo-abiraterone in the BRCAm subgroup (hazard ratio [HR], 0.53; 95% CI, 0.36-0.79; P =.0014) and in the overall HRR population (HR, 0.73; 95% CI, 0.56-0.96; P =.0217) but not in the subgroup of patients with non-BRCA HRR mutations (HR, 0.99; 95% CI, 0.67-1.44).

In an exploratory analysis, the median OS in the BRCAm subgroup was 30.4 months for the niraparib-abiraterone arm and 28.6 months for the placebo-abiraterone arm (HR, 0.79; 95% CI, 0.55-1.12). Among patients with non-BRCA HRR mutations, the HR for OS was 1.13 (95% CI, 0.77-1.64).

The improvement observed with the combination therapy in the HRR gene-mutated population was primarily attributed to the results seen in the subgroup of patients with BRCAm.

As for safety, the most common adverse reactions (≥20%) reported were decreased hemoglobin, 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.

Overall, 27% of patients required a red blood cell transfusion, with 11% requiring multiple transfusions. Increased ALT, edema, dyspnea, decreased appetite, vomiting, dizziness, COVID-19, headache, abdominal pain, hemorrhage, urinary tract infection, cough, insomnia, increased bilirubin, decreased weight, arrhythmia, fall, and pyrexia were also observed (≥10%).

Akeega is supplied as a tablet in 2 dosage strengths: niraparib at 50 mg/abiraterone acetate at 500 mg and niraparib at 100 mg/abiraterone acetate at 500 mg.

The FDA has also approved the use of the FoundationOne CDx as a companion diagnostic for Akeega. Patients should be selected for treatment based on the presence of a BRCA gene alteration.

References

US Food and Drug Administration. FDA approves niraparib and abiraterone acetate plus prednisone for BRCA-mutated metastatic castration-resistant prostate cancer. Accessed August 14, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-niraparib-and-abiraterone-acetate-plus-prednisone-brca-mutated-metastatic-castration.

US FDA approves Akeega^™ (niraparib and abiraterone acetate), the first-and-only dual action tablet for the treatment of patients with BRCA-positive metastatic castration-resistant prostate cancer. Janssen. News release. August 11, 2023. Accessed August 14, 2023. https://www.prnewswire.com/news-releases/us-fda-approves-akeega-niraparib-and-abiraterone-acetate-the-first-and-only-dual-action-tablet-for-the-treatment-of-patients-with-brca-positive-metastatic-castration-resistant-prostate-cancer-301899028.html.

This article originally appeared on MPR