Results from the Phase 3 AMPLITUDE study show the potential of AKEEGA® (niraparib and abiraterone acetate dual-action tablet) to delay cancer progression and worsening of symptoms
Data show a nearly 50 percent reduction in disease progression in BRCA-altered mCSPC vs. current standard of care
CHICAGO, JUNE 3, 2025 – Johnson & Johnson announced today first results from the Phase 3, randomized, double-blind, placebo-controlled AMPLITUDE study evaluating the combination of niraparib and abiraterone acetate plus prednisone (AAP) in patients with metastatic castration-sensitive prostate cancer (mCSPC) with homologous recombination repair (HRR) genetic alterations including BRCA. The results show a clinically meaningful and statistically significant improvement in both radiographic progression-free survival (rPFS) and time to symptomatic progression (TSP), with an early trend toward improved overall survival (OS)—highlighting the potential of the combination in this patient population to delay both cancer progression and the worsening of symptoms.1 This marks the first Phase 3 data to show clinical improvement with a PARP-based combination in mCSPC. The findings are being presented as a late-breaking oral presentation (Abstract #LBA5006) at the 2025 American Society of Clinical Oncology Annual Meeting. The data have also been selected for Best of ASCO and included in the ASCO Press Program.
“Approximately 25 percent of patients with mCSPC have HRR alterations, with about half being BRCA. These patients typically experience faster disease progression and poorer outcomes,” said Gerhardt Attard*, M.D., Ph.D., FRCP, John Black Charitable Foundation Chair of Medical Oncology, University College London Cancer Institute, Research Department of Oncology and presenting author. “The AMPLITUDE trial is the first to show that combining a PARP inhibitor with an androgen receptor pathway inhibitor both delays disease progression and postpones the onset of symptoms in HRR-altered mCSPC, supporting this combination as a new treatment option for these patients.”
“Our aim with the AMPLITUDE study was to determine how long patients could live without their cancer worsening. What we found is that the combination of niraparib, abiraterone acetate, and prednisone is achieving just that, with the goal of offering patients precious quality time before the disease enters a more resistant phase,” said Charles Drake, M.D., Ph.D., FAAP, Vice President, Prostate Cancer and Immunotherapy Disease Area Leader, at Johnson & Johnson Innovative Medicine. “This breakthrough highlights the need for early initiation of personalized treatment strategies for patients with mCSPC and HRR alterations, particularly BRCA, who typically face more aggressive disease.”
The Phase 3 AMPLITUDE study of 696 patients with mCSPC and HRR alterations met its primary endpoint of rPFS. Patients with BRCA alterations (n=191) showed the greatest benefit of treatment with the combination of niraparib plus AAP, as the median rPFS was not reached compared to 26 months in patients treated with the placebo plus AAP, reducing the risk of radiographic progression or death by 48 percent (hazard ratio [HR] 0.52, 95 percent confidence interval [CI], 0.37-0.72, p<0.0001). In patients with any HRR alteration treated with the niraparib combination, median rPFS was also not reached in comparison to 29.5 months in patients treated with the placebo plus AAP, with a reduction in risk of progression or death by 37 percent (HR 0.63, 95 percent CI, 0.49-0.80, p=0.0001).1
These results also showed that treatment with the niraparib combination reduced the risk of symptomatic progression by 56 percent in patients with BRCA alterations (HR 0.44, 95 percent CI, 0.29-0.68, p=0.0001) and 50 percent in patients with HRR alterations (HR 0.50, 95 percent CI, 0.36-0.69, p<0.0001), meaning that patients experienced a longer delay to worsening symptoms and requiring radiation, surgical intervention, or needing a new anti-cancer therapy. The first interim analysis showed an early trend toward improved overall survival (OS) favoring the niraparib/AAP combination with a reduction in risk of death of 25 percent (HR 0.75, 95 percent CI, 0.51-1.11, p=0.15) in patients with BRCA alterations and 21 percent in HRR alterations (HR 0.79, 95 percent CI, 0.59-1.04, p=0.10); follow-up is ongoing for maturity of the data.1
Grade 3/4 adverse events (AE) were more frequent with the niraparib combination compared to the placebo group (75 percent vs. 59 percent), with anemia and hypertension being the most common; however, treatment discontinuations due to AEs remained low (14.7 percent vs 10.3 percent). To date, the safety profile of niraparib plus abiraterone acetate and prednisone has been consistent with prior experiences.1
New data from the CAPTURE study (Abstract #5094), also being presented at the 2025 ASCO Annual Meeting with simultaneous publication in the Annals of Oncology, reinforce that the presence of HRR, specifically BRCA alterations, among patients with mCSPC are associated with significantly worse prognosis. Despite the availability of life-prolonging ARPIs, patients with HRR-altered mCSPC experience approximately 30 percent faster disease progression and shorter survival, while patients with BRCA-altered mCSPC experience approximately 50 percent faster disease progression and shorter survival—highlighting the importance of genetic testing to inform treatment decisions and the urgent need for novel targeted therapies to improve outcomes and delay progression.2
Johnson & Johnson has nearly 20 years of leadership in prostate cancer, treating more than 750,000 patients worldwide. With the AMPLITUDE study, Johnson & Johnson becomes the first to show that a PARP inhibitor combination can benefit patients with mCSPC.3
About AMPLITUDE
AMPLITUDE (NCT04497844) is an ongoing, phase 3, randomized, double-blind, placebo-controlled, international study evaluating the efficacy and safety of niraparib and abiraterone acetate in a dual-action tablet (DAT) formulation with prednisone plus androgen deprivation therapy (ADT) compared to matching oral placebo/abiraterone acetate with prednisone plus ADT in patients with deleterious germline or somatic homologous recombination repair (HRR) gene-altered metastatic castration-sensitive prostate cancer (mCSPC). The primary endpoint is radiographic progression-free survival (rPFS).
About Metastatic Castration-Sensitive Prostate Cancer
Metastatic castration-sensitive prostate cancer (mCSPC), also known as metastatic hormone-sensitive prostate cancer (mHSPC), refers to prostate cancer that still responds to ADT and has spread to other parts of the body.4
About AKEEGA® (niraparib and abiraterone acetate)
AKEEGA® is a combination, in the form of a dual-action tablet (DAT), of niraparib, a highly selective poly (ADP-ribose) polymerase (PARP) inhibitor, and abiraterone acetate, a CYP17 inhibitor. AKEEGA® together with prednisone or prednisolone was approved in April 2023 by the European Medicines Agency, and in August 2023 by the U.S. FDA, for the treatment of patients with BRCA-mutated metastatic castration-resistant prostate cancer (mCRPC). Patients are selected for therapy based on an FDA-approved test for genetic alterations. Additional marketing authorization applications are under review across a number of countries globally.
Additional ongoing studies include the Phase 3 AMPLITUDE study evaluating AKEEGA® with prednisone or prednisolone in a biomarker-selected patient population with metastatic castration-sensitive prostate cancer (mCSPC).
In April 2016, Janssen Biotech, Inc. entered a worldwide (except Japan) collaboration and license agreement with TESARO, Inc. (acquired by GlaxoSmithKline [GSK] in 2019) for exclusive rights to niraparib in prostate cancer.
About Johnson & Johnson
At Johnson & Johnson, we believe health is everything. Our strength in healthcare innovation empowers us to build a world where complex diseases are prevented, treated, and cured, where treatments are smarter and less invasive, and solutions are personal. Through our expertise in Innovative Medicine and MedTech, we are uniquely positioned to innovate across the full spectrum of healthcare solutions today to deliver the breakthroughs of tomorrow, and profoundly impact health for humanity.
Footnotes
*Dr. Attard has provided consulting, advisory, and speaking services to Johnson & Johnson; he has not been paid for any media work.
1 Attard, G., et al. (2025, May). Phase 3 AMPLITUDE trial: Niraparib and abiraterone acetate plus prednisone for metastatic castration-sensitive prostate cancer patients with alterations in homologous recombination repair genes. Presented at the American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago, IL.
2 Olmos, D. (2025, May). Impact of somatic/germline homologous recombination repair (HRR) alterations on metastatic hormone-sensitive prostate cancer (mHSPC) outcomes by disease volume. Presented at the American Society of Clinical Oncology (ASCO) Annual Meeting 2025.
3 Fizazi K, Tran N, Fein L, Matsubara N, Rodriguez-Antolin A, Alekseev BY, Özgüroğlu M, Ye D, Feyerabend S, Protheroe A, Sulur G, Luna Y, Li S, Mundle S, Chi KN. Abiraterone acetate plus prednisone in patients with newly diagnosed high-risk metastatic castration-sensitive prostate cancer (LATITUDE): final overall survival analysis of a randomised, double-blind, phase 3 trial. Lancet Oncol. 2019 May;20(5):686-700. doi: 10.1016/S1470-2045(19)30082-8. Epub 2019 Apr 12. PMID: 30987939.
4 American Society of Clinical Oncology. ASCO Answers: Prostate Cancer (2018). http://www.cancer.net/sites/cancer.net/files/asco_answers_guide_prostate.pdf. Accessed May 2025.