FDA Approves First Fixed-Dose Combination of Niraparib and Abiraterone Acetate for First-Line Treatment of BRCA-Mutated Metastatic Castration-Resistant Prostate Cancer

On August 11, the FDA approved Johnson & Johnson's Akeega (niraparib + abiraterone acetate) for marketing, in combination with prednisone or prednisolone for the first-line treatment of patients with BRCA-mutated metastatic castration-resistant prostate cancer (mCRPC). This is the first and only dual-action tablet approved by the FDA for this indication.

The combination of Niraparib (a highly selective PARP inhibitor) and Abiraterone Acetate (a CYP17 inhibitor), along with Prednisone, targets two oncogenic drivers in mCRPC patients—the androgen receptor axis and HRR gene alterations. BRCA mutation is one type of homologous recombination repair (HRR) gene alteration.

In April 2016, Johnson & Johnson entered into a collaboration with TESARO (which has been acquired by GSK) to obtain global (excluding Japan) development and commercialization rights for niraparib in prostate cancer indications. In April this year, Akeega has been approved in the United States, while it is still under review in China.

This approval is based on the results of the Phase III MAGNITUDE study. MAGNITUDE is a randomized, double-blind, placebo-controlled Phase III clinical trial designed to evaluate the efficacy and safety of niraparib combined with abiraterone acetate and prednisone (AAP) versus placebo combined with AAP as first-line treatment in patients with mCRPC with or without homologous recombination repair (HRR) gene mutations. The trial enrolled 423 patients (including 225 patients with BRCA mutations), with the primary endpoint being radiographic progression-free survival (rPFS).

The results of the first interim analysis showed that rPFS was significantly prolonged in HRR-positive patients (16.5 vs 13.7 months; HR=0.73). In patients carrying BRCA1/2 gene mutations, rPFS was significantly prolonged in the niraparib plus AAP group (16.6 vs 10.9 months; HR=0.53).

At the second interim analysis, the rPFS of patients carrying BRCA1/2 gene mutations had been extended to 19.5 months.

Prostate cancer is one of the most common malignant tumors in men. According to the data published by the World Health Organization (WHO) Cancer Today, the number of new cases of prostate cancer in men worldwide in 2020 was 1,414,259, accounting for 14.1% of all malignant tumors. Its incidence rate is second only to lung cancer, and its mortality rate is 6.8%, ranking fifth. The incidence of prostate cancer in China is also increasing year by year.

A significant proportion of patients already have metastases at the time of initial diagnosis. Currently, the first-line treatment for patients with advanced metastatic prostate cancer is endocrine therapy. However, after a median period of 18 to 24 months, almost all patients will progress to metastatic castration-resistant prostate cancer (mCRPC), with a poor prognosis. Approximately 10-15% of mCRPC patients carry BRCA1/2 gene mutations.

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