Johnson & Johnson's AKEEGA Shows Promise in Metastatic Castration-Sensitive Prostate Cancer

Johnson & Johnson's AKEEGA, a PARP inhibitor combination, has shown a 48% reduction in disease progression for BRCA-altered mCSPC patients and a 37% risk reduction for HRR-altered mCSPC patients in the Phase 3 AMPLITUDE study. AKEEGA is the first PARP-based combination to demonstrate clinical improvement in mCSPC. While there was a higher frequency of Grade 3/4 adverse events, the treatment's safety profile is consistent with prior experiences.

Johnson & Johnson has reported promising results from the Phase 3 AMPLITUDE study, which evaluated the efficacy of AKEEGA® (niraparib and abiraterone acetate dual-action tablet) in patients with metastatic castration-sensitive prostate cancer (mCSPC) with homologous recombination repair (HRR) genetic alterations, including BRCA. The study, presented at the 2025 American Society of Clinical Oncology Annual Meeting, showed a clinically significant improvement in both radiographic progression-free survival (rPFS) and time to symptomatic progression (TSP) [1].

The combination therapy, which includes niraparib, a PARP inhibitor, and abiraterone acetate, plus prednisone, demonstrated a nearly 50 percent reduction in disease progression in BRCA-altered mCSPC compared to the current standard of care. For patients with any HRR alteration, the risk of radiographic progression or death was reduced by 37 percent. These findings are particularly notable as they represent the first Phase 3 data to show clinical improvement with a PARP-based combination in mCSPC [1].

The study enrolled 696 patients with mCSPC and HRR alterations, with approximately 25 percent of patients having HRR alterations, including about half being BRCA. The median rPFS for BRCA-altered patients treated with the niraparib combination was not reached, compared to 26 months in patients treated with the placebo plus AAP. The risk of symptomatic progression was also reduced by 56 percent in BRCA-altered patients and 50 percent in patients with any HRR alteration [1].

While the treatment was associated with a higher frequency of Grade 3/4 adverse events (75 percent vs. 59 percent), the safety profile of niraparib plus abiraterone acetate and prednisone remained consistent with prior experiences. Anemia and hypertension were the most common adverse events, with treatment discontinuations due to AEs remaining low (14.7 percent vs. 10.3 percent) [1].

The AMPLITUDE study highlights the potential of AKEEGA as a new treatment option for patients with mCSPC and HRR alterations, particularly BRCA, who typically face more aggressive disease. The findings underscore the importance of early initiation of personalized treatment strategies for these patients and the urgent need for novel targeted therapies to improve outcomes and delay progression [1].

References:
[1] https://www.investor.jnj.com/news/news-details/2025/Johnson--Johnson-leads-with-first-PARP-inhibitor-combo-to-improve-efficacy-in-patients-with-HRR-altered-mCSPC/default.aspx