FDA approves niraparib in combination with abiraterone acetate plus prednisone for metastatic castra

On December 12, 2025, the U.S. Food and Drug Administration (FDA) approved niraparib in combination with abiraterone acetate (brand name: Akeega, Janssen Biotech, Inc.) plus prednisone for the treatment of adult patients with metastatic castration-sensitive prostate cancer harboring a deleterious or suspected deleterious BRCA2 mutation, as identified by an FDA-approved test.

About the AMPLITUDE Trial

The assessment of efficacy was based on the AMPLITUDE trial (NCT04497844), a randomized, double-blind trial conducted in 696 patients with metastatic castration-sensitive prostate cancer and homologous recombination repair (HRR) gene mutations. Patients were randomly assigned (1:1) to receive niraparib plus abiraterone acetate and prednisone, or placebo plus abiraterone acetate and prednisone. All patients continued to receive androgen deprivation therapy.

The primary efficacy endpoint was investigator-assessed radiographic progression-free survival (rPFS). Overall survival (OS) was another efficacy endpoint.

Trial results showed that in the overall population of patients with HRR mutations, treatment with niraparib plus abiraterone acetate and prednisone demonstrated a statistically significant improvement in rPFS compared with placebo plus abiraterone acetate and prednisone. In an exploratory analysis of 323 patients with BRCA2 mutations, the hazard ratio (HR) for rPFS was 0.46 (95% confidence interval [CI]: 0.32, 0.66). The median rPFS was not estimable (95% CI: 41, not estimable) in the niraparib combination group, versus 26 months (95% CI: 18, 28) in the placebo combination group. In an exploratory analysis of 373 patients without BRCA2 mutations, the HR for rPFS was 0.88 (95% CI: 0.63, 1.24), indicating that the overall improvement was primarily attributable to the results observed in BRCA2-mutated patients.

In the first interim OS analysis in BRCA2-mutated patients, a total of 91 deaths occurred, with 36 (22%) in the niraparib combination group and 55 (34%) in the placebo combination group.

About Warnings and Precautions

The prescribing information includes warnings and precautions for the following conditions: myelodysplastic syndrome/acute myeloid leukemia; myelosuppression; hypokalemia; fluid retention and cardiovascular adverse events; hepatotoxicity; adrenal insufficiency; hypoglycemia; increased risk of fractures and death when used with radium-223 dichloride; posterior reversible encephalopathy syndrome; and embryo-fetal toxicity.

Recommended Dosage

The recommended dosage is niraparib 200 mg and abiraterone acetate 1000 mg orally once daily, in combination with prednisone 5 mg once daily, until disease progression or unacceptable toxicity occurs. Patients should also receive a gonadotropin-releasing hormone (GnRH) analog concomitantly or have undergone bilateral orchiectomy.

Accelerated Review Programs

This review utilized an assessment aid, a voluntary submission by the applicant to facilitate the FDA’s evaluation.

The application was granted priority review designation. FDA’s accelerated programs are detailed in the industry guidance Accelerated Programs for Drugs and Biologics for Serious Conditions.