Janssen Submits NDA for Combo Tablet for Metastatic Prostate Cancer

Janssen Pharmaceutical has submitted a new drug application (NDA) to the FDA seeking approval of niraparib/abiraterone as a dual-action tablet to treat patients with BRCA-positive metastatic castration-resistant prostate cancer (mCRPC). If approved, this will be the first dual-action tablet formulation for patients with mCRPC with BRCA mutations, which are a type of homologous recombination repair (HRR) gene alteration.

Metastatic castration-resistant prostate cancer is a cancer that has spread beyond the prostate gland and has progressed despite medical or surgical treatment to lower testosterone. The most common metastatic sites are bones, followed by lungs and liver. About 10% to 50% of patients progress to mCRPC within three years of diagnosis, of which an estimated 10% to 15% harbor a BRCA mutation. Patients with mCRPC and HRR gene alterations are more likely to have aggressive disease, poor outcomes and a shorter survival time.

The combination of niraparib, a highly selective poly (ADP-ribose) polymerase (PARP) inhibitor, and abiraterone acetate, a prodrug of abiraterone, a CYP17 inhibitor, plus prednisone, targets two oncogenic drivers in patients with mCRPC: the androgen receptor axis and HRR gene alterations. Through the dual action tablet formulation, this therapeutic option may help improve compliance and reduce pill burden.

Peter Lebowitz, M.D., Ph.D.

“Patients with mCRPC and BRCA mutations face a more aggressive form of prostate cancer and high unmet needs in terms of treatment options. The data supporting this submission reinforce the importance of biomarker testing to identify the subgroups of patients that are most likely to respond to a targeted treatment option,” Peter Lebowitz, M.D., Ph.D., global therapeutic area head, oncology, Janssen Research & Development, said in a press release.

The NDA is supported by data from the MAGNITUDE study, a phase 3 study evaluating the safety and efficacy of the combinational therapy as a first-line treatment in patients with mCRPC, with or without alterations in HRR associated genes.

First results from MAGNITUDE were presented at the American Society of Clinical Oncology – Genitourinary Cancers Symposium (ASCO GU) 2022 Annual Meeting for the primary endpoint of investigator-evaluated radiographic progression-free survival (rPFS) in all HRR-positive patients, as well as patients with BRCA mutations, receiving niraparib plus AAP. This analysis found the median radiographic progression-free survival for the therapy combination was 19.5 months compared with 10.9 months for placebo. Additionally, a trend toward improvement in overall survival (OS) was observed in the BRCA subgroup.

Results from the secondary interim analysis were presented at the ASCO GU 2023 Annual Meeting. In IA2, at 26.8 months of median follow-up, researchers further reviewed time to symptomatic progression and time-to-initiation of cytotoxic chemotherapy in the HRR-positive population and the BRCA subgroup. At 18.6-month median follow-up, patients in the combination arm of the cohort with HRR gene alterations showed a significant improvement in rPFS, with a reduction in the risk of progression or death of 27%.