Approval for AKEEGA® is based on results from the Phase 3 MAGNITUDE study, a prospectively designed precision medicine study that includes the largest cohort to date of BRCA1/2-positive patients with untreated metastatic castration-resistant prostate cancer (mCRPC).1,2
Niraparib in combination with abiraterone acetate (AA), plus prednisone or prednisolone, significantly improved radiographic progression-free survival (rPFS) compared to standard of care in untreated mCRPC patients with BRCA1/2 mutations. 3
DUBLIN, Ireland, August 2023 – The Janssen Pharmaceutical Companies of Johnson & Johnson have announced that the European Commission (EC) has granted marketing authorisation for AKEEGA® (niraparib and abiraterone acetate [AA]), in the form of a dual action tablet (DAT), given with prednisone orprednisolone, for the treatment of adults with metastatic castration-resistant prostate cancer (mCRPC) and BRCA1/2 mutations (germline and/or somatic) in whom chemotherapy is not clinically indicated.2
Prostate cancer is one of the most common cancers in men in Ireland with about 3,940 men diagnosed each year.4 Despite treatment advances, mCRPC remains an incurable, deadly disease.5,6BRCA1/2 gene mutations have been identified in approximately 10-15 percent of mCRPC patients 7,8and are more likely to cause aggressive disease, poor outcomes, and a shorter survival time.9,10,11,12
Professor Ray McDermott, Consultant Medical Oncologist, St Vincent’s University Hospital, Dublin said, “Metastatic castration-resistant prostate cancer remains a lethal disease, with high unmet needs in terms of treatment options, particularly for patients with BRCA1/2 gene mutations. The development of innovative therapies is vital to provide patients with new treatment options. The dual action tablet of niraparib with abiraterone acetate is a promising first line targeted treatment option for men with mCRPC and BRCA1/2 mutations. With BRCA testing now publicly available in Ireland, I hope this medicine will reach the right patients at the right time when available here.”
The EC authorisation, which also marks the first worldwide approval for AKEEGA®, is based on results of the randomised, double-blind, placebo controlled, Phase 3 MAGNITUDE study (NCT03748641).13 The trial assessed whether the addition of niraparib to AAP improved outcomes in those with untreated mCRPC, with or without alterations in homologous recombination repair (HRR) associated genes (which are involved in the repair of damaged DNA), including BRCA1/2.1,13 A total of 423 patients with HRR gene alterations were enrolled, 225 (53.2 percent) of whom had BRCA mutations, making it the largest cohort of BRCA1/2-positive patients with first line mCRPC in any clinical study to date.14
Dr Thorsten Giesecke, General Manager, Commercial Business, Janssen Sciences Ireland UC, said: “Janssen’s legacy in innovation and the development of treatments for prostate cancer spans more than a decade. We remain committed to harnessing the power of science to bring solutions to patients at every stage of their cancer journey. The MAGNITUDE trial was prospectively designed as a precision medicine study to identify the specific population of patients who would most benefit from niraparib with AAP, and potentially increase the likelihood of treatment success. This approval marks an exciting step in the right direction, changing the outlook for patients with mCRPC for the better.”
The primary endpoint for MAGNITUDE was radiographic progression-free survival (rPFS), as analysed by blinded central review.1,13 Niraparib plus AAP significantly improved rPFS in all HRR-positive patients (Hazard Ratio [HR] 0.73; 95 percent Confidence Interval [CI], 0.56 to 0.96; p=0.022).3 This improvement was most pronounced in patients with BRCA1/2 gene mutations, where a statistically significant 47 percent risk reduction was observed for rPFS.3 With additional median follow-up at 24.8 months in the BRCA subgroup, rPFS by central review demonstrated a consistent and clinically meaningful treatment effect favouring niraparib plus AAP, with a median rPFS of 19.5 months compared with 10.9 months for placebo plus AAP.1 Additionally, there was a trend towards improved overall survival (OS) with niraparib plus AAP, strong improvement in time to symptomatic progression (TSP) and clinically meaningful improvement in time-to-initiation of cytotoxic chemotherapy (TCC).1
The observed safety profile of the combination of niraparib and AAP was consistent with the known safety profile of each agent.3 Of the patients with HRR gene alterations, 67 percent experienced Grade 3/4 adverse events (AEs) in the combination arm versus 46.4 percent in the control arm.15The most common grade 3 AEs were anaemia (28.3 percent versus 7.6 percent) and hypertension (14.6 percent versus 12.3 percent) with niraparib and AAP versus placebo and AAP, respectively.15The combination of niraparib and AAP also maintained overall quality of life in comparison with placebo and AAP.3,15
Niraparib is a highly selective poly adenosine diphosphate-ribose polymerase (PARP) inhibitor.13Together with AA plus prednisone, the combination DAT regimen targets two oncogenic drivers in patients with mCRPC, namely alterations in the androgen receptor axis and in BRCA1/2.13,16,17 This is the first DAT formulation available in the European Union for patients with mCRPC with BRCA mutations.2
Europe is the first region to approve AKEEGA® (niraparib and abiraterone acetate DAT), for the treatment of patients with BRCA-positive mCRPC, globally. In February 2023, Janssen submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) seeking approval of this niraparib-based combination for the treatment of patients with BRCA-positive mCRPC.18
