FDA approval summary
On December 12, 2025, the U.S. Food and Drug Administration (FDA) approved niraparib and abiraterone acetate (Akeega, Janssen Biotech, Inc.) with prednisone for adult patients with deleterious or suspected deleterious BRCA2-mutated (BRCA2m) metastatic castration-sensitive prostate cancer (mCSPC), as determined by an FDA-approved test.
All patients should receive ongoing androgen deprivation therapy (ADT) with a gonadotropin-releasing hormone (GnRH) analog or have undergone bilateral orchiectomy. Full prescribing information for Akeega will be available on Drugs@FDA.
- Indication: Adults with deleterious or suspected deleterious BRCA2m mCSPC
- Regimen: Niraparib + abiraterone acetate + prednisone, on top of medical or surgical castration
AMPLITUDE trial (NCT04497844)
Efficacy was evaluated in AMPLITUDE (NCT04497844), a randomized, double-blind, placebo-controlled phase 3 trial in patients with homologous recombination repair gene–mutated (HRRm) mCSPC.
- Design: Randomized (1:1), double-blind, multicenter study
- Population: 696 patients with HRRm mCSPC
- Treatment arms:
- Niraparib + abiraterone acetate + prednisone (AAP)
- Placebo + AAP
- All patients received continued ADT
The major efficacy outcome measure was investigator-assessed radiographic progression-free survival (rPFS). Overall survival (OS) was an additional efficacy endpoint.
Key efficacy results: benefit concentrated in BRCA2-mutated disease
AMPLITUDE demonstrated a statistically significant improvement in rPFS with niraparib + AAP versus placebo + AAP in the overall HRRm population. Exploratory subgroup analyses showed that the observed benefit was primarily driven by patients with BRCA2 mutations.
- BRCA2-mutated subgroup (n=323):
- Hazard ratio (HR) for rPFS: 0.46 (95% CI: 0.32, 0.66)
- Niraparib + AAP: median rPFS not estimable (NE)
- 95% CI: 41 months, NE
- Placebo + AAP: median rPFS 26 months (95% CI: 18, 28)
- Non-BRCA2-mutated subgroup (n=373):
- HR for rPFS: 0.88 (95% CI: 0.63, 1.24)
- These data suggest that the overall rPFS improvement is largely attributable to the BRCA2m subgroup.
At the first interim OS analysis in the BRCA2m population, 91 deaths had occurred, including 36 (22%) in the niraparib + AAP arm and 55 (34%) in the placebo + AAP arm.
Safety profile and key warnings
The prescribing information for Akeega includes warnings and precautions for:
- Myelodysplastic syndrome/acute myeloid leukemia (MDS/AML)
- 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 (PRES)
- Embryo-fetal toxicity
In routine practice, careful monitoring of blood counts, liver function, electrolytes (especially potassium), cardiovascular status, and steroid-related metabolic effects will be important, particularly in older or comorbid patients.
Recommended dosing
The recommended dose is as follows:
- Niraparib 200 mg orally once daily
- Abiraterone acetate 1,000 mg orally once daily (taken on an empty stomach)
- Prednisone 5 mg orally once daily
Treatment should be continued until disease progression or unacceptable toxicity. Patients should also receive a GnRH analog concurrently or have undergone bilateral orchiectomy.
Regulatory considerations: priority review and Assessment Aid
- This review used the Assessment Aid, a voluntary submission from the applicant intended to facilitate the FDA’s assessment.
- The application was granted priority review.
- FDA’s expedited programs for serious conditions (e.g., Fast Track, Breakthrough Therapy, Priority Review, Accelerated Approval) are described in the guidance “Expedited Programs for Serious Conditions – Drugs and Biologics.”
Editorial perspective (Morningglorysciences)
The combination of a PARP inhibitor with abiraterone has already attracted attention in metastatic castration-resistant prostate cancer (mCRPC). With this approval, niraparib + abiraterone + prednisone moves into the metastatic castration-sensitive (mCSPC) setting, specifically for patients with BRCA2-mutated disease.
The AMPLITUDE data underscore that the magnitude of rPFS benefit is largely confined to the BRCA2-mutated subgroup, whereas non-BRCA2 HRR alterations show a more modest and statistically non-significant effect. Clinically, this reinforces the concept of a biomarker-driven strategy in which PARP inhibitor–based intensification is prioritized for BRCA2m mCSPC rather than broadly applied to all HRRm patients.
At the same time, clinicians must navigate overlapping toxicities from niraparib (notably hematologic toxicity) and abiraterone + prednisone (metabolic and cardiovascular adverse events), on top of long-term ADT-related effects on bone and cardiometabolic health. In older or comorbid patients, shared decision-making around treatment intensity, quality of life, and long-term risk–benefit balance will be critical.
Key questions going forward include:
- How different HRR alterations beyond BRCA2 (e.g., BRCA1, ATM, PALB2) modulate benefit from this regimen
- How prior use of PARP inhibitors at the mCSPC stage will impact subsequent therapy options in mCRPC
- Real-world patterns of toxicity, dose modification, and treatment discontinuation with prolonged use
Overall, this approval further anchors molecularly defined, PARP inhibitor–based intensification as a cornerstone option for BRCA2-mutated prostate cancer, now extending its reach into the castration-sensitive metastatic setting.
*This article is based on the AACR “FDA Approval Alert” and FDA source materials, summarized and edited by Morningglorysciences.*
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