On December 12, 2025, the U.S. Food and Drug Administration (FDA) approved niraparib in combination with abiraterone acetate and prednisone (AKEEGA®, Janssen Biotech, Inc.) for the treatment of adult patients with deleterious or suspected deleterious BRCA2-mutated metastatic castration-sensitive prostate cancer (mCSPC), as determined by an FDA-approved test.
This approval expands the role of PARP inhibition into the castration-sensitive setting and establishes a new targeted treatment option for patients with BRCA2-mutated disease. Full prescribing information for AKEEGA will be available on Drugs@FDA.
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Efficacy Based on the AMPLITUDE Trial
The FDA approval was based on results from AMPLITUDE (NCT04497844), a randomized, double-blind, placebo-controlled Phase III trial that enrolled 696 patients with homologous recombination repair gene-mutated (HRRm) metastatic castration-sensitive prostate cancer.
Patients were randomized 1:1 to receive either:
- Niraparib plus abiraterone acetate and prednisone (AAP)
or
- Placebo plus AAP
All patients continued androgen deprivation therapy (ADT) throughout the study.
The primary efficacy endpoint was investigator-assessed radiographic progression-free survival (rPFS). Overall survival (OS) was a key secondary endpoint.
Key Efficacy Results
The AMPLITUDE trial demonstrated a statistically significant improvement in rPFS for niraparib plus AAP compared with placebo plus AAP in the overall HRRm population.
However, prespecified exploratory analyses showed that the clinical benefit was primarily driven by patients with BRCA2 mutations.
Among the 323 patients with BRCA2-mutated mCSPC, the results were as follows:
- Hazard ratio for rPFS: 0.46
- 95% confidence interval: 0.32–0.66
- Median rPFS: Not estimable (95% CI: 41 months to not estimable) with niraparib plus AAP
- Median rPFS: 26 months (95% CI: 18–28) with placebo plus AAP
In contrast, in the 373 patients with non-BRCA2 HRR mutations, the rPFS benefit was not statistically significant:
- Hazard ratio for rPFS: 0.88
- 95% confidence interval: 0.63–1.24
These findings indicate that the overall treatment effect in the trial was largely attributable to patients with BRCA2-mutated disease.
Overall Survival Interim Analysis
At the time of the first interim overall survival analysis, a total of 91 deaths had occurred in the BRCA2-mutated population:
- 36 deaths (22%) in the niraparib plus AAP arm
- 55 deaths (34%) in the placebo plus AAP arm
While OS data are not yet mature, this early trend supports a potential survival benefit with the combination in BRCA2-mutated mCSPC.
Safety and Warnings
The prescribing information for AKEEGA includes warnings and precautions consistent with the known safety profiles of niraparib and abiraterone. Key risks include:
- Myelodysplastic syndrome and acute myeloid leukemia
- Myelosuppression
- Hypokalemia
- Fluid retention and cardiovascular adverse reactions
- Hepatotoxicity
- Adrenocortical insufficiency
- Hypoglycemia
- Increased fractures and mortality when combined with radium Ra 223 dichloride
- Posterior reversible encephalopathy syndrome
- Embryo-fetal toxicity
Patients receiving this regimen require close monitoring, particularly for hematologic, cardiovascular, and hepatic adverse events.
Recommended Dosing
The FDA-approved recommended dose is:
- Niraparib 200 mg orally once daily
- Abiraterone acetate 1,000 mg orally once daily
- Prednisone 5 mg orally once daily
Treatment should continue until disease progression or unacceptable toxicity. Patients should also receive a gonadotropin-releasing hormone (GnRH) analog concurrently or have undergone bilateral orchiectomy.
Clinical Significance
This FDA approval represents a significant advancement in the management of BRCA2-mutated metastatic castration-sensitive prostate cancer, bringing precision therapy earlier in the disease course. By integrating PARP inhibition with androgen signaling blockade, niraparib plus abiraterone offers a genetically targeted option for a patient population with historically aggressive disease biology.