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

The Food and Drug Administration (FDA) has approved Akeega^™ (niraparib and abiraterone acetate) for the treatment of adult patients 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 poly (ADP-ribose) polymerase (PARP) inhibitor, and abiraterone acetate, a CYP17 inhibitor into a single tablet. The approval was based on data from the randomized, placebo-controlled, double-blind, phase 3 MAGNITUDE study (ClinicalTrials.gov Identifier: NCT03748641).

Study participants with homologous recombination repair (HRR) gene-mutated (HRRm) mCRPC (Cohort 1) were randomly assigned to receive niraparib 200mg and abiraterone 1000 mg (n=212) or placebo and abiraterone (n=211) until unacceptable toxicity or progression. All patients received prednisone 10mg daily and a gonadotropin-releasing hormone (GnRH) analog or had prior bilateral orchiectomy. In this study population, 53% (n=225) had BRCA gene mutations. The primary endpoint was radiographic progression free survival (rPFS); overall survival (OS) was an additional outcome measure.

Findings showed a statistically significant improvement in rPFS with niraparib plus abiraterone compared with placebo plus abiraterone in the BRCAm subgroup (hazard ratio, 0.53 [95% CI, 0.36-0.79]; P =.0014). In the overall HRR population, the rPFS HR was 0.73 (95% CI, 0.56-0.96; P =.0217), while in the subgroup of patients with non-BRCA HRR mutations (n=198), the rPFS HR was 0.99 (95% CI, 0.67-1.44).

In an exploratory analysis, median OS in the BRCAm subgroup was reported to be 30.4 months (95% CI, 27.6, not estimable) for the niraparib plus abiraterone arm and 28.6 months (95% CI, 23.8-33.0) for the placebo plus abiraterone arm (OS HR, 0.79 [95% CI, 0.55-1.12). Among patients with non-BRCA HRR mutations, the OS HR was 1.13 (95% CI, 0.77-1.64).

“As a physician, identifying patients with a worse prognosis is a priority, especially those whose cancers have a BRCA mutation,” said Kim Chi, MD, Medical Oncologist at BC Cancer – Vancouver and principal investigator of the phase 3 MAGNITUDE study. “We prospectively designed the MAGNITUDE study to identify the subset of patients most likely to benefit from targeted treatment with Akeega and to help us understand how we can potentially achieve better health outcomes for patients.”

Findings from the study indicate that 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.

In the MAGNITUDE study, 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 50mg/abiraterone acetate 500mg and niraparib 100mg/abiraterone acetate 500mg.

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.