EU approval for dual action prostate cancer therapy

European Commission

The European Commission (EC) has granted marketing authorisation for Akeega (niraparib and abiraterone acetate [AA]) for adults with metastatic castration-resistant prostate cancer (mCRPC) and BRCA1/2 mutations (germline and/or somatic).

The drug is given in the form of a dual action tablet (DAT), with prednisone or prednisolone, and is approved in patients for whom chemotherapy is not clinically indicated.

Despite treatment advances, mCRPC remains an incurable, deadly disease. BRCA1/2 gene mutations have been identified in approximately 10-15% of mCRPC patients and are more likely to cause aggressive disease, poor outcomes, and a shorter survival time.

“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 MAGNITUDE study

The EC authorisation, which also marks the first worldwide approval for Akeega, is based on results of the randomised, double-blind, placebo controlled, Phase III MAGNITUDE study.

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, including BRCA1/2.

A total of 423 patients with HRR gene alterations were enrolled, 225 (53.2%) 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.

The primary endpoint for MAGNITUDE was radiographic progression-free survival (rPFS), as analysed by blinded central review. This improvement was most pronounced in patients with BRCA1/2 gene mutations, where a statistically significant 47% risk reduction was observed for rPFS.

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. 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).

“This European milestone 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, Global Therapeutic Area Head, Oncology, Janssen Research & Development, LLC.

Niraparib is a highly selective poly adenosine diphosphate-ribose polymerase (PARP) inhibitor. 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.

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