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

pharmafile | April 24, 2023 | News story | Business Services  

BEERSE, Belgium, 21 April 2023 – The Janssen Pharmaceutical Companies of Johnson & Johnson announced today 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 or prednisolone, 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 the most common cancer in men in Europe, and the sixth-highest cause of cancer-related death worldwide. 4,5 Despite treatment advances, mCRPC remains an incurable, deadly disease. 6,7 BRCA1/2 gene mutations have been identified in approximately 10-15 percent of mCRPC patients8,9 and are more likely to cause aggressive disease, poor outcomes, and a shorter survival time. 10,11,12,13

“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,” said Professor Gerhardt Attard, Oncologist, University College London (UCL), London, UK*. “We’ve seen that in these patients, niraparib combined with abiraterone acetate and predniso(lo)ne (AAP) significantly reduced the risk of disease progression or death compared to AAP. 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.”

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). 14 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. 1,14 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. 15

“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 abiraterone acetate plus predniso(lo)ne, and potentially increase the likelihood of treatment success,” said Martin Vogel, EMEA Therapeutic Area Lead Oncology, Janssen Cilag GmbH. “The results, on which this European Commission approval is based, reinforce the benefit of this niraparib-based combination in effectively addressing BRCA mutations and changing the outlook for patients with mCRPC.”

The primary endpoint for MAGNITUDE was radiographic progression-free survival (rPFS), as analysed by blinded central review.1,14 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 intime 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.16 The 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. 16 The combination of niraparib and AAP also maintained overall quality of life in comparison with placebo and AAP.3,16

“This European milestone, which also marks the first worldwide approval for AKEEGA®, highlights the value of precision medicine and the importance of genetic testing in patients with mCRPC to ensure the right patients receive the right treatment,” said Peter Lebowitz, M.D., Ph.D., Global Therapeutic Area Head, Oncology, Janssen Research & Development, LLC. “It also demonstrates our ongoing commitment at Janssen to developing innovative therapeutic approaches to help improve outcomes for patients living with prostate cancer.”

Niraparib is a highly selective poly adenosine diphosphate-ribose polymerase (PARP) inhibitor.14 Together 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. 14,17,18 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. 19

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