FDA Approves New Combination Therapy for BRCA-Positive Metastatic Castration-Resistant Prostate Cancer


Niraparib and abiraterone acetate (Akeega; Janssen Pharmaceutical Companies of Johnson & Johnson) is the first-and-only dual action tablet that combines a PARP inhibitor with abiraterone acetate administered with prednisone.

The FDA has approved niraparib and abiraterone acetate (Akeega; Janssen Pharmaceutical Companies of Johnson & Johnson) for the treatment of adults with deleterious or suspected deleterious BRCA-positive, metastatic castration-resistant prostate cancer (mCRPC) as detected by an FDA-approved test. The treatment is the first-and-only dual action tablet that combines a poly (ADP-ribose) polymerase (PARP) inhibitor with abiraterone acetate administered with prednisone.1

“The approval of Akeega brings an important treatment option to patients with prostate cancer as they consider their road ahead, and it also highlights the importance of genetic testing and precision medicine for this disease,” said Shelby Moneer, MS, CHES, vice president of Patient Programs and Education, ZERO Prostate Cancer, in a press release.1 “All individuals diagnosed with prostate cancer should consider genetic testing, especially those from racial and ethnic minority groups who tend to have worse cancer outcomes. This is imperative to close the racial and ethnic disparities in prostate cancer health outcomes.”

Akeega is once daily, dual action tablet (DAT) consisting of niraparib, a highly selective PARP inhibitor, and abiraterone acetate, an androgen biosynthesis inhibitor. The novel DAT combination targets 2 oncogenic drivers in patients with mCRPC and HRR gene alterations. The approval of Akeega was based on positive findings from the randomized, double-blind, placebo-controlled, multi-center, phase 3 MAGNITUDE trial.

The trial enrolled patients with (HRR biomarker [BM] positive; ATM, BRCA1, BRCA2, BRIP1, CDK12, CHEK2, FANCA, HDAC2, PALB2) and without specified gene alterations (HRR BM negative) to receive niraparib 200 mg once daily plus AAP or placebo plus AAP. Among 423 patients enrolled with HRR gene alterations, 225 (53.2%) had BRCA mutations.

The MAGNITUDE trial’s primary endpoint was radiographic progression-free survival (rPFS) as assessed by blinded independent central review. Secondary endpoints included time to initiation of cytotoxic chemotherapy (TCC), time to symptomatic progression (TSP), and overall survival (OS).

Among BRCA-positive patients administered the combination of Akeega plus prednisone, researchers reported a statistically significant 47% risk reduction in rPFS (Hazard ratio [HR], 0.53; p=0.001). Further, a second interim analysis of rPFS with a median follow-up of 24.8 months in the BRCA-positive patient subgroup showed a consistent trend in favor of Akeega plus prednisone, with a median rPFS of 19.5 months vs 10.9 months in the placebo and AAP group (HR, 0.55 [95% confidence interval (CI), 0.39-0.78]).

Further, the findings showed improved secondary endpoints in TSP (HR, 0.54 [95% CI, 0.35-0.85]) and TCC (HR, 0.56 [95% CI, 0.35-0.90]) for patients in the Akeega plus prednisone cohort compared with AAP alone, which was supported by a trend toward improved OS (HR, 0.88 [95% CI, 0.58-1.34]), according to the investigators.

In terms of adverse events (AEs), the safety profile of the Akeega plus prednisone combination was consistent with the known safety profile for each FDA-approved monotherapy. Among patients in the MAGNITUDE trial with a BRCA gene alteration, 41% who were administered the combination experienced a serious AE.

The most common AEs that occurred in 20% or more of patients administered Akeega plus prednisone compared with patients administered placebo and AAP were musculoskeletal pain (44% vs 42%, respectively), fatigue (43% vs 30%), constipation (34% vs 20%), hypertension (33% vs 27%), and nausea (33% vs 21%). Fifteen percent of patients experienced an AE causing permanent discontinuation of any component of the Akeega combination.

“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.”


U.S. 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 Pharmaceutical Companies of Johnson & Johnson. News release. August 11, 2023. https://www.janssen.com/fda-approves-akeega-niraparib-and-abiraterone-acetate-first-and-only-dual-action-tablet

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