Niraparib/Abiraterone Acetate Dual Action Tablet Approaches EU Approval in mHSPC With BRCA1/2 Mutations

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion regarding an indication extension for the use of niraparib and abiraterone acetate (Akeega) with prednisone or prednisolone (AAP) paired with androgen deprivation therapy (ADT) in patients with metastatic hormone-sensitive prostate cancer (mHSPC) and germline and/or somatic BRCA1/2 mutations. ¹

The recommendation is supported by data from the phase 3 AMPLITUDE study (NCT04497844), which were shared during the 2025 ASCO Annual Meeting, and indicated that niraparib plus AAP led to a median radiographic progression-free survival (rPFS) that was not reached vs 26.0 months with placebo plus AAP in those with BRCA1/2 mutations (n = 191), translating to a 48% reduction in the risk of radiographic progression or death (HR, 0.52; 95% CI, 0.37-0.72; P < .0001). Niraparib/AAP also significantly prolonged time to symptomatic progression by 56% vs placebo/AAP (HR, 0.44; 95% CI, 0.29-0.68; P = .0001). Data from the first interim analysis of the study suggested an early trend toward improved overall survival (OS) favoring niraparib/AAP in this subset (HR, 0.75; 95% CI, 0.51-1.11; P = .15).

“Patients with mHSPC who carry BRCA1/2 mutations face a more aggressive disease with survival outcomes that are significantly shorter, compared to those without these mutations, with limited treatment options before their disease progresses to [mHSPC],” Henar Hevia, PhD, senior Director, EMEA Therapeutic Area Head of Oncology at Johnson & Johnson Innovative Medicine, stated in a news release.¹ “Pending approval, the niraparib and abiraterone acetate dual-action tablet will offer a targeted treatment strategy with the potential to address this urgent medical need earlier in the metastatic pathway, before the disease becomes more resistant.”

How was the AMPLITUDE study designed?

AMPLITUDE is a phase 3, randomized, double-blind, placebo-controlled, international, multicenter study that enrolled patients with mHSPC and an alteration in at least 1 homologous recombination repair–eligible gene.^1,2 Participants (n = 696) were randomly assigned 1:1 to receive placebo (n = 348) or 200 mg of niraparib (n = 348) once daily plus AAP at 1000 mg once daily and 5 mg once daily and ADT. The primary end point is rPFS by investigator review, and important secondary end points included time to symptomatic progression, OS, and safety.

What safety findings were observed with niraparib plus AAP in this population?

Treatment-emergent adverse effects (TEAEs) occurred in more than 99% of patients who received niraparib plus AAP vs 98% of those given placebo plus AAP (n = 348); these effects were treatment related in 89% and 74% of patients, respectively. Grade 3 or 4 TEAEs were reported in 75% of those who received niraparib plus AAP and 59% of those given placebo/AAP; they were related to treatment for 56% and 30% of patients, respectively. Serious toxicities were reported in 39% and 28% of patients, respectively. TEAEs led to dose reduction, treatment discontinuation, or proved fatal for 22%, 15%, and 4% of patients in the niraparib arm, respectively; in the placebo arm, these respective rates were 7%, 10%, and 2%.

In the niraparib plus AAP arm, 88% of patients experienced at least 1 adverse effect (AE) of special interest; this effect was grade 3 or higher in severity for 63% of patients. Hematologic AEs of special interest included anemia (all grade, 52%; grade ≥ 3, 29%), neutropenia (22%; 10%), thrombocytopenia (19%; 7%), and myelodysplastic syndrome (<1%; <1%). Cardiovascular AEs of special interest included hypertension (45%; 27%), arrhythmia (20%; 5%), and cardiac failure (6%; 3%). Other AEs of special interest were hypokalemia (27%; 12%) and hepatotoxicity (13%; 2%).

What is the clinical significance of the news?

“Building on our deep legacy spanning nearly two decades in the treatment of prostate cancer, we are driven by the belief that the next frontier of care requires more personalized treatment approaches that address the specific drivers of high-risk disease,” Charles Drake, MD, PhD, FAAP, vice president and Prostate Cancer and Immunotherapy disease area leader at Johnson & Johnson Innovative Medicine, added in the news release.¹ “The combination of niraparib and abiraterone acetate represents an important step towards integrating targeted precision medicine into routine care, complementing our established apalutamide plus ADT option, a proven standard of care for the broader mHSPC patient population, reinforcing our commitment to delivering solutions across the prostate cancer continuum.”

References

1. Johnson & Johnson receives CHMP positive opinion for AKEEGA® (niraparib and abiraterone acetate dual action tablet) for the treatment of patients with metastatic hormone-sensitive prostate cancer (mHSPC) with BRCA1/2 mutations. News Release. Janssen Cilag. January 30, 2026. Accessed January 30, 2026. https://www.globenewswire.com/news-release/2026/01/30/3229458/0/en/Johnson-Johnson-receives-CHMP-positive-opinion-for-AKEEGA-niraparib-and-abiraterone-acetate-dual-action-tablet-for-the-treatment-of-patients-with-metastatic-hormone-sensitive-prost.html
2. A study of niraparib in combination with abiraterone acetate and prednisone vs 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. Updated January 22, 2026. Accessed January 30, 2026. https://clinicaltrials.gov/study/NCT04497844
3. Attard G, Agarwal N, Graff J, et al. Phase 3 AMPLITUDE trial: niraparib (NIRA) and abiraterone acetate plus prednisone (AAP) for metastatic castration-sensitive prostate cancer (mCSPC) patients (pts) with alterations in homologous recombination repair (HRR) genes. J Clin Oncol. 2025;43 (suppl 17):LBA5006. doi:10.1200/JCO.2025.43.17_suppl.LBA5006