FDA Approves Ensacove for ALK+ NSCLC Treatment

Manufactured by Xcovery Holdings Inc and Betta Pharmaceuticals, ensartinib’s new drug application was accepted by the FDA in March 2024  The approval is based on the results from eXalt3 (NCT02767804), a phase III randomized study that compared ensartinib with crizotinib among patients with ALK-positive NSCLC. Patients were enrolled if they had not received any form of prior treatment with an ALK inhibitor.

A total of 290 patients were randomized to receive either 225 mg of ensartinib once daily or 225 mg of crizotinib twice daily. PFS was the primary outcome, and overall survival (OS) was the main secondary outcome. Ensartinib had significant improvements in PFS compared with crizotinib (HR, 0.56; 95% CI, 0.4-0.79; P = .0007), demonstrating a statistically superior median PFS compared with crizotinib (25.8 months vs 12.7 months). No statistically significant differences were reported for OS (HR, 0.88; 95% CI, 0.63-1.23; P = .457). Adverse events (AEs) associated with ensartinib occurred in no more than 10% of the patient population. Common AEs were mainly grade 2 or less, and included rash, elevated transaminase levels, pruritus, nausea, constipation, edema, anemia, vomiting, decreased appetite, and increases to blood alkaline phosphatase, blood creatinine, and g-glutamyltransferase. Health care professionals recommend ensartinib dosage as 225 mg orally once daily, either with or without food, until disease progression halts or unacceptable toxicity is reached.

Crizotinib is a first-generation ALK inhibitor, and the first ALK inhibitor to treat patients with NSCLC.  Second-generation ALK inhibitors include ceritinib, alectinib, brigatinib, and ensartinib, while lorlatinib is considered third generation. Both second- and third-generation ALK inhibitors are more potent than crizotinib, and often associated with higher frequency of ALK-resistance mutations