Takeda's ALK Inhibitor Brigatinib Receives CDE Acceptance for Market Application in China, Recommended as First-Line Therapy by NCCN Guidelines

On January 21, the CDE website showed that Takeda Pharmaceutical submitted a marketing application for the Class 5.1 imported new drug Brigatinib, which was accepted.

Brigatinib (also known as布吉他滨 or 布加替尼) is an ALK inhibitor. In the latest guidelines for non-small cell lung cancer (NSCLC) released by the U.S. National Comprehensive Cancer Network (NCCN) at the end of 2020, brigatinib was recommended as the preferred first-line treatment for ALK-positive advanced NSCLC.

Brigatinib (trade name ALUNBRIG), developed by Ariad, a subsidiary of Takeda Pharmaceutical Company Limited, received accelerated approval from the U.S. Food and Drug Administration (FDA) in April 2017 for the treatment of patients with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) who had experienced disease progression or intolerance to crizotinib. In May 2020, it was approved by the U.S. FDA as a first-line treatment for adult patients with ALK-positive metastatic NSCLC.

The FDA’s approval of brigatinib as a first-line treatment for ALK-positive NSCLC was based on the results of the ALTA-1L study. The ALTA-1L study is a Phase III, open-label, randomized controlled clinical trial that head-to-head compared the efficacy and safety of brigatinib versus crizotinib as first-line therapy in patients with advanced NSCLC harboring ALK fusions. In previously untreated patients with ALK-positive NSCLC, the brigatinib group demonstrated a significantly improved progression-free survival (PFS) rate compared with the crizotinib group, with 1-year PFS rates of 67% versus 43%, respectively, representing a 51% reduction in the risk of disease progression or death (HR: 0.49). The objective response rates (ORR) were 71% versus 60%, respectively.

Based on these findings, brigatinib and alectinib are jointly recommended as preferred first-line treatments for ALK-positive NSCLC in the newly released NCCN guidelines.

Furthermore, brigatinib has demonstrated surprising therapeutic potential as a later-line treatment. At the 2020 ASCO Annual Meeting, researchers presented the primary analysis results of the pivotal J-ALTA clinical trial. This study enrolled a total of 72 patients from 28 centers across Japan, including 47 patients who had previously been treated with alectinib and/or crizotinib. The data showed an overall response rate (ORR) of 30.6%, a disease control rate (DCR) of 78.7%, a median progression-free survival (PFS) of 7.3 months, and an intracranial ORR of 25%.

These results indicate that brigatinib retains a certain degree of efficacy in patients with alectinib resistance harboring mutations such as G1202R, I1171N, L1152R, L1198F, and V1180L.

Insight database shows that Takeda first submitted a clinical trial application in China in August 2018, with the initial clinical trial public disclosure made in March 2019, and today marks its first submission of a marketing authorization application.

Brigatinib Project Details ▼

From the Insight database (http://db.dxy.cn/v5/home/)