Janssen Announces Zejula (Niraparib) in Combination with Abiraterone and Prednisone Demonstrates Significant Efficacy in First-Line Treatment of HRR-Mutated mCRPC

News on February 15, 2022 /BioValleyBIOON/ -- Johnson & Johnson (JNJ) subsidiary Janssen Pharmaceuticals recently in the United States clinicalTumorPreliminary data from the Phase 3 MAGNITUDE study (NCT03748641) of the PARP inhibitor class anticancer drug Zejula (Chinese brand name: Zele, generic name: niraparib) for the treatment of metastatic castration-resistant prostate cancer (mCRPC) was presented at the American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU).

MAGNITUDE is a randomized, double-blind, placebo-controlled, multicenter study designed to evaluate the safety and efficacy of Zejula in combination with Zytiga (abiraterone acetate) and prednisone for the first-line treatment of patients with mCRPC. The study includes two independent cohorts with the aim of assessing the therapeutic effect of the Zejula + Zytiga + prednisone regimen compared to standard of care (Zytiga + prednisone regimen) in patients with or without homologous recombination repair (HRR) gene alterations (including ATM, BRCA1, BRCA2, BRIP1, CDK12, CHEK2, FANCA, HDAC2, PALB2 alterations).

The prospective cohort study enrolled 423 patients with HRR gene alterations, who were randomly assigned to receive either the Zejula+Zytiga+prednisone regimen (combination group [n=212]) or the placebo+Zytiga+prednisone regimen (control group [n=211]). After a median follow-up of 18.6 months,In the cohort with HRR gene alterations, the radiological progression-free survival (rPFS) of patients in the combination group was significantly improved, with a 27% reduction in the risk of disease progression or death (HR=0.73; p=0.022).. This kind ofThe improvement was most pronounced in patients with BRCA1/2 gene alterations., according to the blinded independent central review (BICR) analysis,The risk of rPFS was reduced by 47%.(HR 0.53; p=0.001). A consistent but greater improvement was observed in investigator-assessed rPFS, showing a 36% overall risk reduction in patients with HRR gene alterations (HR: 0.64; p=0.002) and a 50% risk reduction in patients with BRCA1/2 gene alterations (HR: 0.50; p=0.0006).

August 2020,The cohort without HRR gene alterations (n=233) met the pre-defined futility criteria, indicating no benefit of combination therapy in the HRR biomarker-negative population (HR>1).. Based on the recommendation of the independent data monitoring committee, enrollment in this cohort was stopped due to lack of efficacy. Investigators and patients were unblinded and had the option to continue treatment with Zejula + Zytiga + prednisone regimen or, at the investigator’s discretion, receive only the Zytiga + prednisone regimen.

In patients with HRR gene alterations, the first interim analysis of secondary endpoints also demonstrated clinically relevant improvements in outcomes, including time to initiation of cytotoxic chemotherapy, time to symptom progression, and time to PSA progression. Additionally, treatment with Zejula + Zytiga + prednisone improved the objective response rate. In this interim analysis, overall survival (OS) data remain immature, and follow-up for all secondary endpoints will continue.The safety of the Zejula+Zytiga+prednisone regimen observed in this study is consistent with the known safety profile of each drug.

Patients with HRR gene alterations (such as BRCA1/2) have an increased risk of developing prostate cancer, and BRCA-associated prostate cancers are typically aggressive. Patients with mCRPC have a low long-term survival rate, and those with HRR gene alterations have an even worse prognosis, leading to a significant unmet medical need for new therapies in this disease.

The data released this time indicateProstate cancer patients with HRR gene alterations who received the Zejula + Zytiga + prednisone regimen experienced clinically meaningful improvements in outcomes. These patients may benefit from this combination regimen, highlighting the importance of biomarkers in guiding treatment decisions.

The active pharmaceutical ingredient in Zejula is niraparib, an oral, highly selective poly ADP-ribose polymerase (PARP) inhibitor that exploits deficiencies in DNA repair pathways to preferentially kill cancer cells. This mechanism of action gives the drug the potential to treat a wide range of tumors with DNA repair defects. PARP is associated with a broad spectrum ofTumorType-related, especiallyBreast CancerAnd ovarian cancer.

Zejula, developed by Tesaro, is a potential best-in-class PARP inhibitor due to its differentiated efficacy, once-daily dosing, and superior pharmacokinetic properties, including its ability to cross the blood-brain barrier.

In April 2016, Janssen, a subsidiary of Johnson & Johnson, signed a global (excluding Japan) collaboration and license agreement with Tesaro, obtaining exclusive rights to Zejula for the treatment of prostate cancer. At the end of September 2016, Zai Lab entered into a license agreement with Tesaro, securing the rights to Zejula in mainland China, Hong Kong, and Macao. In December 2018,GSKFor $5.1 billion (approximately £4 billion), Tesaro was acquired. (Bioon.com)

Source of Original Text:Janssen Presents New Data Demonstrating the Combination of Niraparib and Abiraterone Acetate Plus Prednisone Significantly Improved Radiographic Progression-Free Survival as a First-Line Therapy in Patients with HRR Gene-Mutated Metastatic Castration-Resistant Prostate Cancer