EU Approval Is Sought for Niraparib/Abiraterone Acetate Dual-Action Tablet in mHSPC With HRR Gene Alterations

An extension of indication application has been submitted to the European Medicines Agency (EMA) seeking the approval of a dual-action tablet (Akeega)—comprising niraparib (Zejula) and abiraterone acetate (Zytiga)—in combination with prednisone or prednisolone for the treatment of adult patients with metastatic hormone-sensitive prostate cancer (mHSPC) harboring homologous recombination repair (HRR) gene alterations.¹

The application is supported by data from the phase 3 AMPLITUDE trial (NCT04497844). Findings presented at the 2025 ASCO Annual Meeting showed that patients with HRR-mutated mHSPC treated with niraparib plus abiraterone, prednisone, and androgen-deprivation therapy (ADT; n = 348) achieved a median radiographic progression-free survival (rPFS) that was not evaluable (NE) compared with 29.5 months for those given placebo plus abiraterone, prednisone, and ADT (n = 348; HR, 0.63; 95% CI, 0.49-0.80; P = .0001).² In patients harboring BRCA mutations, the median rPFS was NE in the niraparib arm (n = 191) vs 26.0 months in the placebo arm (n = 196; HR, 0.52; 95% CI, 0.37-0.72; P < .0001).

“Despite significant progress in prostate cancer, individuals with HRR gene alterations often face limited treatment options, faster onset of symptoms, and poorer outcomes,” Henar Hevia, PhD, senior director and the EMEA Therapy Area head of Oncology at Johnson & Johnson Innovative Medicine, stated in a 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.”

In August 2023, the FDA approved the dual-action formulation of niraparib and abiraterone acetate in combination with prednisone for the treatment of adult patients with deleterious or suspected deleterious BRCA-positive, metastatic castration-resistant prostate cancer (mCRPC), as detected by an FDA-approved test.³ Previously, in April 2023, the European Commission approved the dual-action combination plus prednisone or prednisolone (AAP) for adult patients with BRCA1/2-mutated mCRPC in whom chemotherapy is not clinically indicated.⁴

These prior approvals were based on data from the phase 3 MAGNITUDE trial (NCT03748641).^3,4

Diving into AMPLITUDE

The randomized, double-blind, placebo-controlled study enrolled patients with mHSPC harboring at least 1 HRR gene mutation, such as BRCA1/2, BRIP1, CDK12, CHEK2, FANCA, PALB2, RAD51B, and RAD54L.² Patients also needed to have an ECOG performance status of 0 to 2. Patients were excluded if they had received any prior treatment with a PARP inhibitor or an androgen receptor pathway inhibitor other that abiraterone. Permitted prior therapies included ADT (for no more than 6 months), docetaxel (for no more than 6 cycles), AAP (for no more than 45 days), and palliative radiotherapy.

Patients were randomly assigned 1:1 to receive niraparib at 200 mg per day plus abiraterone at 1000 mg per day, prednisone at 5 mg per day, and ADT; or placebo plus the same dosing of abiraterone, prednisone, and ADT.

Key stratification factors comprised HRR mutation status (BRCA2 vs CDK12 vs all other alterations), prior docetaxel (yes vs no), and disease volume (high vs low).

Along with the primary end point of rPFS, secondary end points included time to symptomatic progression (TTSP), overall survival (OS), and safety.

Additional Efficacy and Safety Findings

The median TTSP was NE in both the niraparib and placebo arms in the HRR-mutated population (HR, 0.50; 95% CI, 0.36-0.69; P < .0001). Within the BRCA-mutated population, the median TTSP was also NE in both groups (HR, 0.44; 95% CI, 0.29-0.68; P = .0001).

Although OS data were immature, trends favored the niraparib regimen in the HRR-mutated population (HR, 0.79; 95% CI, 0.59-1.04; P = .10) and the BRCA-mutated population (HR, 0.75; 95% CI, 0.51-1.11; P = .15).

Regarding safety, treatment-emergent adverse effects (TEAEs) of any grade occurred in more than 99% of evaluable patients in the niraparib arm (n = 347) and 98% of patients in the placebo arm (n = 348). The rates of any-grade treatment-related TEAEs were 89% and 74%, respectively. Grade 3/4 TEAEs were reported in 75% of patients in the experimental arm vs 59% of patients in the placebo group. The respective rates of grade 3/4 treatment-related TEAEs were 56% and 30%. The rates of serious AEs were 39% and 28%, respectively, with 13% and 3% of patients, respectively, experiencing treatment-related serious AEs.

In the niraparib arm, TEAEs led to treatment discontinuation, dose reductions, and death in 15%, 22%, and 4% of patients, respectively. These respective rates were 10%, 7%, and 2% in the placebo arm.

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):LBA5006. doi:10.1200/JCO.2025.43.17_suppl.LBA5006
3. U.S. FDA approves Akeega (niraparib and abiraterone acetate), the first-and-only dual action tablet for the treatment of patients with BRCA-positive metastatic castration-resistant prostate cancer. News release. Janssen. August 11, 2023. Accessed July 7, 2025. https://www.jnj.com/media-center/press-releases/u-s-fda-approves-akeega-niraparib-and-abiraterone-acetate-the-first-and-only-dual-action-tablet-for-the-treatment-of-patients-with-brca-positive-metastatic-castration-resistant-prostate-cancer
4. Janssen marks first approval worldwide for Akeega (niraparib and abiraterone acetate dual action tablet) with EC authorisation for the treatment of patients with metastatic castration resistant prostate cancer with BRCA1/2 mutations. News release. Janssen. April 21, 2023. Accessed July 7, 2025. https://www.jnj.com/media-center/press-releases/janssen-marks-first-approval-worldwide-for-akeega-niraparib-and-abiraterone-acetate-dual-action-tablet-with-ec-authorization-for-the-treatment-of-patients-with-metastatic-castration-resistant-prostate-cancer-with-brca1-2-mutations