Janssen's Dual-Action Combination Therapy Akeega (Niraparib/Abiraterone) Approved in China for BRCA-Mutated mCRPC

China Finance and Economics News, October 21st: Johnson & Johnson announced today that its innovative therapeutic drug Zebeke (Niraparib Abiraterone Tablets) has officially been approved by the National Medical Products Administration.

As the first and only dual-action combination therapy approved in China, Zebec combined with prednisone or prednisolone is used to treat adult patients with metastatic castration-resistant prostate cancer (mCRPC) carrying germline and/or somatic BRCA gene mutations.

Zejula is a first-line targeted treatment option for adult patients with BRCA1/2-mutated mCRPC. As a highly selective poly (ADP-ribose) polymerase (PARP) inhibitor, the combination of niraparib and abiraterone acetate with prednisone or prednisolone can target two oncogenic drivers in mCRPC patients—the androgen receptor axis and BRCA1/2 mutations. Clinical trials have validated that Zejula in combination with prednisone or prednisolone significantly prolongs radiographic progression-free survival (rPFS) in BRCA1/2-mutated mCRPC patients. Additionally, compared to placebo, niraparib also demonstrated a trend toward overall survival (OS) improvement, significantly extending time to symptomatic progression (TSP) and time to initiation of cytotoxic chemotherapy (TCC), while maintaining patients' quality of life.

Data shows that in recent years, the incidence of prostate cancer in China has risen significantly. According to the latest 2022 China Malignant Tumor Disease Burden Report released by the National Cancer Center, the incidence rate of prostate cancer in China is 18.61 cases per 100,000 people, making it the most common tumor in the male urinary and reproductive systems.

Despite the improvement in China's medical standards and certain progress in the treatment of prostate cancer, mCRPC remains a fatal disease. Statistics show that approximately 10-15% of mCRPC patients carry BRCA1/2 gene mutations. Prostate cancer with BRCA1/2 gene mutations is often more malignant, potentially more aggressive, and associated with a higher proportion of metastatic disease, leading to poorer survival outcomes for patients. Therefore, authoritative guidelines both in China and internationally, such as those from NCCN and EAU, recommend genetic testing for mCRPC patients to provide more precise treatment decisions and improve clinical benefits for patients.

Cherry Huang, President of Johnson & Johnson Innovative Pharmaceuticals China, stated that the approval of Zebec underscores the arrival of the era of precision treatment for prostate cancer and highlights the significant role of genetic testing in the diagnosis and treatment of prostate cancer. "For a long time, Johnson & Johnson has consistently focused on the real needs of prostate cancer patients at different stages of the disease, continuously introducing innovative therapies and product portfolios, expanding from late-stage treatment of prostate cancer to earlier stages. At the same time, we also hope to enable more patients to achieve comprehensive management of prostate cancer, gaining longer survival through early, standardized, and full-course diagnosis and treatment."

The approval of Zebeke this time is based on the MAGNITUDE multicenter phase III study, which was randomized, double-blind, and placebo-controlled. The results showed that in the BRCA-mutated subgroup, Niraparib combined with Abiraterone Acetate plus Prednisone or Prednisolone (AAP) significantly reduced the risk of radiographic progression or death by 47% (rPFS, HR=0.53; 95% CI 0.36, 0.79; p=0.0014). At the second interim analysis, the median follow-up time was 24.8 months. Compared with 10.9 months for placebo plus AAP, the median rPFS for Niraparib combined with AAP in the BRCA-mutated subgroup was 19.5 months (HR, 0.55 [95% CI, 0.39-0.78]). In addition, Niraparib demonstrated a statistically significant benefit in time to symptom progression (TSP), reducing the risk of symptom progression by 46% compared to the control group (median not reached vs. 23.6 months; HR=0.54, 95% CI: 0.35-0.85; P=0.0071). Notably, the trial also observed that in patients with mCRPC harboring BRCA1/2 mutations treated with Niraparib plus AAP compared to those receiving placebo plus AAP, Niraparib achieved statistically and clinically meaningful improvement in time to cytotoxic chemotherapy initiation (TCC) (median not reached vs. 27.3 months; HR: 0.56, 95% CI: 0.35-0.90; p=0.0152).

In terms of safety, studies have shown that the combination of niraparib and AAP is consistent with the known safety profiles of the individual drugs. The most common adverse reactions (>10%) of this combination therapy include musculoskeletal pain, fatigue, constipation, hypertension, nausea, edema, dyspnea, etc.