Abiraterone acetate

In castration-sensitive prostate cancer, the Akeega regimen’s magnitude of progression-free survival benefit was notably bigger at 48% in the BRCA-mutated subgroup when compared with the overall trial population. The FDA has already approved PARP inhibitors in certain patients with metastatic castration-resistant prostate cancer (mCRPC). Now, Johnson & Johnson’s Akeega is giving the class a win in castration-sensitive disease, although the drug’s benefit in a patient subgroup remains unclear.In patients with metastatic castration-sensitive prostate cancer (mCSPC) with homologous recombination repair (HRR), Akeega and prednisone significantly reduced the risk of tumor progression or death by 37% versus J&J’s Zytiga and prednisone, according to data shared at the 2025 American Society of Clinical Oncology annual meeting. Akeega is a fixed-dose combination of GSK’s PARP inhibitor Zejula—to which J&J owns prostate cancer rights—and Zytiga.Despite the positive readout from the phase 3 Amplitude trial, saying Akeega has a clear regulatory path ahead in all HRR-mutated mCSPC would be too optimistic.The uncertainty lies in a group of patients without BRCA mutations.Previously, Zejula’s addition to Zytiga and prednisone showed a progression-free survival benefit in HRR-mutated mCRPC in the phase 3 Magnitude trial. But after speaking with the FDA and realizing that the drug was most beneficial in the BRCA-mutated population, J&J filed for—and received—an approval only in that subset of patients. Now, Amplitude is facing the same BRCA/non-BRCA question. Compared with the entire trial population, the Akeega regimen’s magnitude of progression-free survival benefit was notably bigger at 48% in the BRCA-mutated subgroup.“The benefit may be greatest in patients with BRCA alterations,” lead study author Gerhardt Attard, M.D., Ph.D., from University College London, said during a press briefing.The result is still in favor of Akeega in the non-BRCA subgroup, with an improvement of around 20%, Attard noted.“There is efficacy in the non-BRCA subgroup,” Attard said. “It’s heterogeneous, and it’s a number of different smaller gene subgroups.”“You’re going to need to do meta-analysis of multiple different trials to have certainty which subgroup has clear evidence of efficacy.”The non-BRCA subgroup is not small, accounting for 45% of the Amplitude population. Based on the current data, Akeega doesn’t appear to work in patients with the PALB2 mutation, but there are positive trends in other subtypes, Mark Wildgust, Ph.D., vice president of oncology global medical affairs at J&J Innovative Medicine, said in an interview with Fierce Pharma.“Does it have the same magnitude [of benefit as in BRCA]? I do not believe it does,” Wildgust said. “Is there enough there for regulatory approval? Maybe not right now, but maybe in the future. Maybe we have to wait a bit longer to see longer-term follow up and to understand the question.”J&J will have a discussion with global regulators, including the FDA, on whether the Amplitude trial has shown a positive risk-benefit profile in the overall HRR population, Wildgust said.Besides progression-free survival, researchers also identified a positive trend toward improved overall survival in the Akeega arm. However, data here were immature and didn’t meet statistical significance at the current analysis. The preliminary death reduction was 25% in the BRCA-mutated group and 21% in the overall trial population.Editor's Note: The story was updated to clarify the situation around Akeega's mCRPC indication. 

Having secured approval in BRCA-positive metastatic castration-resistant prostate cancer (mCRPC), Johnson & Johnson's Akeega (niraparib/abiraterone) has now produced positive findings in patients with castration-sensitive disease, including an early trend toward improved overall survival (OS). However, the benefit was greater in a subgroup of participants, raising questions about the path forward.The latest data come from the Phase III AMPLITUDE study, which randomised 696 patients with metastatic castration-sensitive prostate cancer (mCSPC) and HRR genetic alterations, including BRCA, to receive Akeega or placebo, both in combination with current standard-of-care consisting of prednisone plus androgen deprivation therapy (ADT). A dual-action tablet, Akeega combines J&J's anti-androgen therapy Zytiga (abiraterone) with GSK's PARP inhibitor Zejula (niraparib).Results presented Tuesday at the American Society of Clinical Oncology (ASCO) annual meeting showed that AMPLITUDE achieved its primary endpoint of radiographic progression-free survival (rPFS). Patients in the Akeega arm had a 37% reduction in the risk of progression or death, which was clinically meaningful and statistically significant versus placebo. Median rPFS was not reached in those on J&J's combo drug, and was 29.5 months in the placebo group.However, in the subgroup of patients with BRCA alterations, the risk of radiographic progression or death was reduced by 48% with Akeega — median rPFS has not been reached in this arm either, and was 26 months for placebo recipients.Further analysis neededLead study author Gerhardt Attard noted that "there is efficacy in the non-BRCA subgroup, but it's heterogeneous and it's a number of different smaller subgroups." Attard said "we're going to need to do meta-analysis on multiple different trials to have certainty which subgroup has clear evidence of efficacy."J&J added that AMPLITUDE also met its key secondary endpoint of time to symptomatic progression, with Akeega reducing the risk of symptomatic progression versus placebo by 50% in the overall trial population, rising to 56% in the subgroup of patients with BRCA alterations. Akeega also showed an early trend toward improved OS at the first interim analysis, with a reduction in risk of death of 21%, increasing to 25% for the BRCA subgroup.In terms of safety, J&J said that Grade 3/4 adverse events (AE) occurred at a rate of 74% in the Akeega arm, compared with 59% for placebo, with anaemia and hypertension being the most common. Meanwhile, treatment discontinuations due to AEs were 14.7% and 10.3% in the two arms, respectively."Our aim with the AMPLITUDE study was to determine how long patients could live without their cancer worsening," explained Charles Drake, prostate cancer and immunotherapy disease area leader, at Johnson & Johnson Innovative Medicine. "What we found is that [Akeega]...and prednisone is achieving just that, with the goal of offering patients precious quality time before the disease enters a more resistant phase."Akeega together with prednisone or prednisolone was approved in 2023 by the European Medicines Agency and the FDA.