The FDA has granted full approval to niraparib + abiraterone acetate with prednisone (Akeega), an oral dual-action therapy targeting DNA repair deficiency and androgen receptor signaling, for adult patients with BRCA2-mutated metastatic castration-sensitive prostate cancer (mCSPC). In the Phase 3 AMPLITUDE trial, this combination significantly improved radiographic progression-free survival (rPFS) and delayed the time to symptomatic progression (TSP) compared with standard abiraterone + prednisone, with benefits primarily driven by BRCA2-mutated patients. Safety was consistent with the known profiles of the individual agents, with specific monitoring recommended for hematologic, hepatic, and cardiovascular risk.
Akeega Profile & Mechanism
- Profile: Poly (ADP-ribose) polymerase (PARP) inhibitor (niraparib) + CYP17 (androgen receptor) inhibitor (abiraterone acetate) to be combined with prednisone.
- Mechanism: Dual targeting of DNA repair deficiency and androgen receptor signaling to delay radiographic and symptomatic disease progression.
- Target Population: Adult patients with BRCA2-mutated metastatic castration-sensitive prostate cancer (mCSPC)
- Delivery System: Oral administration of a dual-action tablet (DAT)
- Treatment Schedule: Once, daily.
- The recommended dose = 200 mg niraparib + 1,000 mg abiraterone acetate in combination with 5 mg prednisone until disease progression/unacceptable toxicity.
- Patients should receive an androgen deprivation therapy (ADT) concurrently or have had a bilateral orchiectomy.
AMPLITUDE Study Design (NCT04497844)
- Study Design: Phase 3, randomized, double-blind, placebo-controlled, multicenter trial.
- Study Objective: Evaluate the efficacy and safety of niraparib + abiraterone acetate DAT in combination with prednisone and ADT against a placebo or abiraterone acetate + prednisone/ADT in patients with mCSPC.
- Participants: Adult patients with deleterious germline/somatic homologous recombination repair (HRR) gene-altered mCSPC.
- Total enrolled: 696 participants across 32 countries
- BRCA2-mutated subgroup was specifically analyzed for efficacy outcomes
- Primary Endpoint: Radiographic Progression-Free Survival (rPFS).
- Secondary Endpoints: Overall Survival (OS) and Time to Symptomatic Progression (TSP).
Study Outcomes
- Primary Endpoint: rPFS
- The trial demonstrated a statistically significant improvement in rPFS with niraparib + abiraterone acetate and prednisone compared with placebo + abiraterone acetate and prednisone in the overall HRR-mutated population.
- BRCA2-mutated subgroup (n = 323)
- HR: 0.46 (95% CI: 0.32-0.66)
- Median rPFS: Not estimateable with niraparib + abiraterone acetate and prednisone versus 26 months (95% CI: 18-28) with placebo + abiraterone acetate and prednisone.
- Non-BRCA2-mutated subgroup (n = 373)
- HR: 0.88 (95% CI: 0.63-1.24)
- Indicates that rPFS benefit in the overall population was primarily driven by patients with BRCA2 mutations.
- Secondary Endpoints: OS + TSP
- OS: Niraparib = 36 deaths (22%) and placebo = 55 deaths (34%).
- TSP: Niraparib prolonged time to symptomatic progression by 59% compared with placebo (HR: 0.41 (95% CI: 0.29-0.65)).
Regulatory Milestones
- Approval Date: December 12, 2025.
- Regulatory Pathway: Approval was based on a Supplemental New Drug Application (sNDA) submitted to and approved by the U.S. FDA.
- Approval Review: Priority review.
Safety
- Warnings and precautions have been included in the prescribing information for the following:
- Myelodysplastic syndrome/acute myeloid leukemia; myelosuppression; hypokalemia; fluid retention and cardiovascular adverse reactions; hepatotoxicity; adrenocortical insufficiency; hypoglycemia; increased fractures and mortality in combination with radium Ra 223 dichloride; posterior reversible encephalopathy syndrome; embryo-fetal toxicity.
- Special Populations: Elderly (≥75 years) individuals have a higher incidence of fatal adverse reactions and should be monitored for severe renal impairment and/or moderate-severe hepatic impairment.
The observed safety profile of niraparib + abiraterone acetate in combination with prednisone was consistent with the known safety profile of each FDA-approved monotherapy.
Prescribing & Safety Reporting Information
- Prescribing information: Available at Drugs@FDA.
- Side Effect Reporting: Healthcare professionals are encouraged to report negative side effects to the FDA
Sources:
“U.S. FDA Approves AKEEGA® as the First Precision Therapy for BRCA2-Mutated Metastatic Castration-Sensitive Prostate Cancer with 54% Reduction in Disease Progression vs Standard of Care*.” JNJ.com, 13 Dec. 2025, www.jnj.com/media-center/press-releases/u-s-fda-approves-akeega-as-the-first-precision-therapy-for-brca2-mutated-metastatic-castration-sensitive-prostate-cancer-with-54-reduction-in-disease-progression-vs-standard-of-care. Accessed 9 Jan. 2026.
Center. “FDA Approves Niraparib and Abiraterone Acetate plus Prednisone.” U.S. Food and Drug Administration, 25 Dec. 2025, www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-niraparib-and-abiraterone-acetate-plus-prednisone-brca2-mutated-metastatic-castration. Accessed 9 Jan. 2026.
“A Study of Niraparib in Combination with Abiraterone Acetate and Prednisone versus Abiraterone Acetate and Prednisone for the Treatment of Participants with Deleterious Germline or Somatic Homologous Recombination Repair (HRR) Gene-Mutated Metastatic Castration-Sensitive Prostate Cancer (MCSPC) (AMPLITUDE).” Clinicaltrials.gov, 5 Dec. 2025, clinicaltrials.gov/study/NCT04497844.
