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 CastrationResistant Prostate Cance

pharmafile | February 20, 2023 | News story | Business Services  

BEERSE, BELGIUM, 16 February 2023 – The Janssen Pharmaceutical Companies of Johnson & Johnson today announced updated results from the Phase 3 MAGNITUDE study evaluating the investigational use of niraparib, a highly selective poly (ADP-ribose) polymerase (PARP) inhibitor, in combination with abiraterone acetate plus prednisone (AAP) in patients with metastatic castration-resistant prostate cancer (mCRPC) with or without specific homologous recombination repair (HRR) gene alterations, including BRCA mutations. 1 Results will be featured in a Rapid Abstract Session (Abstract #170) at the American Society of Clinical Oncology’s Genitourinary (ASCO GU) Cancers Symposium 2023, taking place February 16-18. 1 In the second interim analysis (IA2) of the MAGNITUDE study (NCT03748641), the treatment combination of niraparib and AAP, in comparison to placebo and AAP at 26.8 months of median follow-up, demonstrated a statistically significant prolongation in time to symptomatic progression (TSP) and continued consistent improvement of time-to-initiation of cytotoxic chemotherapy (TCC) in the HRR-positive population and a strong improvement in TSP for the BRCA subgroup of the HRR-positive population. 1,2 Updated radiographic progression free survival (rPFS) results were consistent with the primary analysis which showed statistically significant benefit in both the HRR-positive population and BRCA subgroup.1,2,3 Additionally, a trend toward improvement in overall survival (OS) was observed in the BRCA subgroup. 1,2 No new safety signals were identified. 1,2 The most common adverse events for niraparib and AAP versus placebo and AAP, regardless of causality, were anemia (50.0 percent vs 22.7 percent, respectively), hypertension (33.0 percent vs 22.3 percent) and constipation (33.0 percent vs 15.6 percent). 1,2 Patients without HRR gene alterations had no improvement in outcomes from the use of niraparib in combination with AAP.1,2 “Patients with HRR-positive mCRPC, especially those with BRCA mutations, are more likely to experience poor outcomes. Although additional follow-up for overall survival continues, it is encouraging to see a trend toward improvement in overall survival among patients with BRCApositive mCRPC who received niraparib and AAP as compared to placebo and AAP,” said Kim Chi*, M.D., Medical Oncologist at BC Cancer – Vancouver and principal investigator of the MAGNITUDE study. “Taken together, these data continue to support the potential use of niraparib in combination with AAP in patients with mCRPC and BRCA mutations.” Notably, in the BRCA subgroup (8.1 months additional follow-up at IA2), rPFS by central review demonstrated a consistent and clinically meaningful treatment effect favoring niraparib and AAP, with a median rPFS of 19.5 months at IA2 compared with 10.9 months for placebo and AAP (hazard ratio [HR], 0.55 (95 percent confidence interval [CI], 0.39-0.78). 1,2 For patients with BRCA-positive mCRPC, preplanned sensitivity analysis evaluating rPFS by investigator review also showed benefit for niraparib and AAP (HR, 0.46 [95 percent CI, 0.32- 0.67]). 1,2 Further, results of the IA2 indicate that patients with BRCA mutations treated with niraparib and AAP experienced a trend towards delayed time to worst pain intensity (HR, 0.70 [95 percent CI, 0.44-1.12]) and pain interference (HR, 0.67 [95 percent CI, 0.40-1.12]) compared with placebo and AAP. 1,2  “At Janssen, our goal is to provide treatment options that delay progression, prolong life, and support a better quality of life for those diagnosed with prostate cancer,” said Martin Vogel, EMEA Therapeutic Area Lead for Oncology, Janssen-Cilag GmbH. “The MAGNITUDE study highlights the importance of biomarker testing to identify those who will optimally benefit from the combination of niraparib and AAP. This is a crucial step in ensuring we can bring the right treatment to the right patients, based on their unique characteristics, and speaks to our wider commitment to exploring precision medicine to treat, intercept and prevent, and potentially one day cure, diseases like mCRPC.” “A high unmet need remains for patients living with BRCA-mutated mCRPC. The MAGNITUDE results further demonstrate the potential of niraparib plus abiraterone acetate plus prednisone to overcome the poor prognostic outcome in these patients. These findings underscore the importance of identifying patients with BRCA mutations to better inform treatment strategies and enable the right patients to receive add-on therapy with a PARP inhibitor,” said Mary Guckert, RN, MSN, Vice President, Development Leader, Prostate Cancer, Janssen Research & Development, LLC. “As the treatment landscape for prostate cancer continues to evolve, we are committed to evaluating innovative targeted therapies to help improve outcomes for patients with HRR-positive prostate cancer.” Prostate cancer is the most common cancer in men across Europe. 4 In 2020, more than 473,000 patients were diagnosed in Europe and over 100,000 deaths were attributed to this challenging disease. 5 Patients with mCRPC and HRR gene alterations, of which BRCA mutations are the most common, are more likely to have aggressive disease, poor outcomes and a shorter survival time. 6,7,8,9 Up to 30% percent of mCRPC cancer cases have alterations in genes associated with HRR.3,10 Approximately 10 to 15 percent of patients with mCRPC have BRCA gene alterations.11,12 In April 2022, Janssen submitted a marketing authorisation application to the European Medicines Agency seeking approval for niraparib in combination with abiraterone acetate in the form of a dual action tablet (DAT), plus prednisone or prednisolone, based on data from the MAGNITUDE study.13 Marketing authorisation applications are under review across a number of countries globally.

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