NDA Submitted for Niraparib Plus Abiraterone Acetate + Prednisone for Prostate Cancer

The New Drug Application (NDA) for niraparib in combination with abiraterone acetate, in the form of a dual-action tablet (DAT), plus prednisone, has been submitted to the Food and Drug Administration (FDA) for the treatment of patients with BRCA-positive metastatic castration-resistant prostate cancer (mCRPC).

The application is supported by data from the randomized, placebo-controlled, double-blind, phase 3 MAGNITUDE study (ClinicalTrials.gov Identifier: NCT03748641) that assessed the efficacy and safety of niraparib plus abiraterone acetate and prednisone (AAP) as a first-line treatment in patients with mCRPC with or without alterations in homologous recombination repair (HRR) associated genes. Patients with HRR gene alterations were randomly assigned 1:1 to receive niraparib 200mg once daily plus AAP (n=212) or placebo plus AAP (n=211).

The primary endpoint was rPFS, as assessed by blinded independent central review, in the BRCA1/2 group followed by all HRR-positive patients; rPFS was defined as the time from randomization date to date of radiographic progression or death, whichever occurred first.

In the primary analysis of MAGNITUDE, results showed that treatment with niraparib plus AAP met the primary endpoint reducing the risk of progression or death in the BRCA1/2 subgroup and in all HRR-positive patients after a median follow-up of 18.6 months. Niraparib plus AAP also met key secondary endpoints, including delaying time to initiation of cytotoxic chemotherapy, time to symptomatic progression (TSP), and time to prostate-specific antigen progression. 

In the second interim analysis, treatment with niraparib plus AAP at 26.8 months of median follow-up met the primary endpoint of rPFS with consistent findings to the primary analysis. Moreover, the niraparib plus AAP arm achieved a statistically significant prolongation in TSP and continued improvement of time-to-initiation of cytotoxic chemotherapy in the HRR-positive population, and a strong improvement in TSP for the BRCA subgroup of the HRR-positive population.

As for safety, the most common adverse events for niraparib plus AAP vs placebo plus AAP, regardless of causality, were anemia (50.0% vs. 22.7%, respectively), hypertension (33.0% vs. 22.3%) and constipation (33.0% vs. 15.6%). There was no evidence of benefit from the use of niraparib plus AAP in patients without HRR gene alterations.

“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,” said Peter Lebowitz, MD, PhD, Global Therapeutic Area Head, Oncology, Janssen Research & Development, LLC. “This submission further represents our commitment at Janssen to discover and develop precision medicine approaches and combination therapies to help improve outcomes for patients living with genetically defined disease.”

Niraparib, a poly (ADP-ribose) polymerase (PART) inhibitor, is currently marketed under the trade name Zejula and is indicated for the maintenance treatment in adults with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to first-line platinum-based chemotherapy. It is also indicated for the maintenance treatment in adults with deleterious or suspected deleterious germline BRCA-mutated (gBRCAmut) recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy. 

References

1. Janssen submits New Drug Application to the US Food and Drug Administration seeking approval of niraparib and abiraterone acetate dual-action tablet, plus prednisone, as a first-line targeted treatment for patients with metastatic castration-resistant prostate cancer with BRCA gene mutations. News release. The Janssen Pharmaceutical Companies of Johnson & Johnson. Accessed March 1, 2023. https://www.prnewswire.com/news-releases/janssen-submits-new-drug-application-to-the-us-food-and-drug-administration-seeking-approval-of-niraparib-and-abiraterone-acetate-dual-action-tablet-plus-prednisone-as-a-first-line-targeted-treatment-for-patients-with-metastat-301759480.html?tc=eml_cleartime.
2. Janssen presents updated data demonstrating improved outcomes from the use of niraparib in combination with abiraterone acetate plus prednisone as a first-line therapy in patients with BRCA-positive metastatic castration-resistant prostate cancer. News release. The Janssen Pharmaceutical Companies of Johnson & Johnson. February 16, 2023. Accessed March 1, 2023. https://www.jnj.com/janssen-presents-updated-data-demonstrating-improved-outcomes-from-the-use-of-niraparib-in-combination-with-abiraterone-acetate-plus-prednisone-as-a-first-line-therapy-in-patients-with-brca-positive-metastatic-castration-resistant-prostate-cancer.

This article originally appeared on MPR