Betta Pharmaceuticals: ALK Inhibitor "Ensartinib" Approved by FDA

On December 18, the U.S. FDA officially approved Ensartinib (brand name Ensacove, developed by Xcovery Holdings, Inc.) for marketing, intended for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) who have not previously received ALK inhibitor therapy, and who are positive for anaplastic lymphoma kinase (ALK).

Ensartinib is a novel, highly selective, and potent next-generation ALK inhibitor co-developed by Betta Pharmaceuticals and its subsidiary, Xcovery. In vitro tests have shown that this inhibitor effectively suppresses various ALK mutations.

According to the FDA press release, the approval of Ensacove is mainly based on the positive results of the eXALT3 study. This was an open-label, randomized, active-controlled, multicenter clinical trial that enrolled 290 patients with locally advanced or metastatic ALK-positive NSCLC who had not previously received ALK-targeted treatment. The patients were randomly assigned in a 1:1 ratio to the ensartinib treatment group or the crizotinib treatment group.

The primary efficacy endpoint of the study was progression-free survival (PFS), as assessed by independent central review (ICR). The secondary key efficacy endpoint was overall survival (OS). The results showed that compared to the active control drug, ensartinib significantly extended the PFS of patients, with a hazard ratio (HR) of 0.56 (95% CI: 0.40-0.79; p=0.0007). The median PFS for the ensartinib group was 25.8 months (95% CI: 21.8-not yet reached), while the median PFS for the active control group was 12.7 months (95% CI: 9.2-16.6). However, no statistically significant difference was observed between the two groups in terms of overall survival (HR=0.88, 95% CI: 0.63-1.23; p=0.4570).

The most common adverse reactions (incidence ≥20%) of Ensartinib include rash, musculoskeletal pain, constipation, cough, itching, nausea, edema, fever, and fatigue.

In November 2020, Ensartinib was approved by China's NMPA for the treatment of ALK-positive, locally advanced or metastatic NSCLC patients who had progressed after prior crizotinib treatment or were intolerant to crizotinib (i.e., second-line indications). In March 2022, Ensartinib was approved in China for first-line treatment of non-small cell lung cancer.

The FDA approval of Ensartinib not only provides a new treatment option for ALK-positive NSCLC patients worldwide but also offers new opportunities for the innovative development of the pharmaceutical industry and for investors' investment decisions.