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The application is supported by data from the phase 3 AMPLITUDE trial.
Johnson & Johnson has submitted an application to the European Medicine’s Agency (EMA) seeking an expanded indication for niraparib and abiraterone acetate (Akeega) with prednisone or prednisolone to include use in the treatment of adult patients with metastatic hormone-sensitive prostate cancer (mHSPC) and homologous recombination repair (HRR) gene alterations, Janssen Cilag International NV announced in a news release.1
The AMPLITUDE trial is ongoing.
Niraparib plus AAP was previously approved in Europe in April 2023 for the treatment of patients with metastatic castration-resistant prostate cancer.
“Despite significant progress in prostate cancer, individuals with HRR gene alterations often face limited treatment options, faster onset of symptoms and poorer outcomes,” said Henar Hevia, PhD, senior director, EMEA therapy area head, oncology, Johnson & Johnson Innovative Medicine, in the news release.1 “With this submission to the EMA, we have the opportunity to offer patients with HRR-mutated mHSPC a treatment specifically targeted to the underlying biology of their disease. Pending approval, this niraparib-based combination will help redefine the standard of care for this high-risk population, significantly delaying the time to their cancer progressing. This milestone reflects our commitment to advancing precision medicine in earlier stages of disease.”
The application is supported by data from the phase 3 AMPLITUDE trial (NCT04497844), which showed that the addition of niraparib to standard of care (SOC) abiraterone acetate plus prednisone or prednisolone (AAP) significantly improved radiographic progression-free survival (rPFS) vs SOC alone in patients with mHSPC with HRR gene alterations. The data were presented at the 2025 American Society of Clinical Oncology Annual Meeting in Chicago, Illinois.2
Specifically, the addition of niraparib to AAP was shown to reduce the risk of radiographic progression or death by 37% among patients in the intent-to-treat population (ITT; HRR mutations) and by 48% in patients with BRCA mutations (BRCAm).
Among those with HRR mutations (ITT), the median rPFS was not met in the niraparib plus AAP arm, compared with 29.5 months in the placebo plus AAP arm (HR, 0.63; 95% CI, 0.49 to 0.80; P = .0001). In those with BRCA mutations, the median rPFS was not reached in the niraparib plus AAP arm vs 26 months in the placebo plus AAP arm (HR, 0.52; 95% CI, 0.37 to 0.72; P < .0001).
In total, the AMPLITUDE trial enrolled 696 patients who were randomly assigned to receive 200 mg niraparib plus 1000 mg abiraterone acetate plus 5 mg prednisone once daily (n = 348) or to matched placebo plus 1000 mg abiraterone acetate plus 5 mg prednisone once daily.
Data on the trial’s secondary end points also showed that the addition of niraparib reduced the risk of symptomatic progression by 50% in the ITT population (HR, 0.50; 95% CI, 0.36 to 0.69; P < .0001) and 56% in the BRCAm cohort (HR, 0.44; 95% CI, 0.29 to 0.68; P = .0001). At the time of data report, the median time to symptomatic progression was not reached in either arm in either the ITT population or in the BRCAm population.
Overall survival data were not mature at the time of data report, but favored the niraparib plus AAP arm. The addition of niraparib to AAP was shown to reduce the risk of death by 21% in the HRRm population (HR, 0.79; 95% CI, 0.59 to 1.04; P = .10) and 25% in the BRCAm population (HR, 0.75; 95% CI, 0.51 to 1.11; P = .15).
Grade 3 to 4 treatment-emergent adverse events (AEs) were reported in 75% of patients in the niraparib arm vs 59% in the placebo arm. The investigators also noted a less than 5% increase in the rate of discontinuation due to toxicity with niraparib vs placebo (15% vs 10%, respectively).
The most common grade 3 or higher AE was anemia, reported in 29% of patients in the niraparib arm vs 5% of patients in the placebo arm. Grade 3 or higher hypertension was also reported in 27% of patients in the niraparib arm vs 18% of patients in the placebo arm.
Other common AEs of any grade included constipation (35% vs 16%), nausea (31% vs 14%), fatigue (26% vs 18%), and arthralgia (21% vs 21%) in the niraparib vs placebo arms, respectively.
The AMPLITUDE trial is ongoing, with final completion expected in November 2027.3
“At Johnson & Johnson, we remain committed to addressing the needs of individual patients by pushing the boundaries of science and innovation to deliver more personalized and effective treatment options at every stage of the prostate cancer journey,” said Charles Drake, MD, PhD, FAAP, vice president, prostate cancer and immunotherapy disease area leader, at Johnson & Johnson Innovative Medicine, in the news release.1 “The fixed dose combination of niraparib and abiraterone acetate has already had a positive impact in shifting the treatment paradigm for patients with metastatic castration-resistant prostate cancer, and we now look forward to extending this benefit to those with hormone-sensitive disease.”
REFERENCES
1. Johnson & Johnson submits application to the European Medicines Agency seeking indication extension of AKEEGA (niraparib and abiraterone acetate dual action tablet) for the treatment of adult patients with metastatic hormone-sensitive prostate cancer and HRR gene alterations. News release. Janssen Cilag International NV. July 3, 2025. Accessed July 7, 2025. https://www.jnj.com/media-center/press-releases/johnson-johnson-submits-application-to-the-european-medicines-agency-seeking-indication-extension-of-akeega-niraparib-and-abiraterone-acetate-dual-action-tablet-for-the-treatment-of-adult-patients-with-metastatic-hormone-sensitive-prostate-cancer-and-hrr-gene-alterations
2. 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; abstr LBA5006). Doi: 10.1200/JCO.2025.43.17_suppl.LBA5006
3. 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. Last updated May 23, 2025. Accessed July 7, 2025. https://clinicaltrials.gov/study/NCT04497844
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