The selective tyrosine kinase inhibitor masitinib was effective as an add-on therapy in reducing exacerbations in patients with severe persistent asthma uncontrolled by oral corticosteroids, according to recent research originally released as an abstract for the American Thoracic Society (ATS) Conference 2020.
“Masitinib is a small molecule drug targeting KIT, LYN and FYN. These kinases are involved in the function of dendritic, epithelial, and mast cells, which are implicated in various mechanisms of asthma pathogenesis,” Pascal Chanez, MD, PhD, of Aix Marseille Université in Marseille, France, and colleagues wrote in their study abstract. “[Masitinib] demonstrated a positive benefit/risk ratio over a sustained period and may provide a new treatment option in severe asthma, irrespective of baseline eosinophil level.”
In the prospective, multicenter, double-blind, placebo-controlled, two-parallel groups, phase 3 AB07015 trial, 404 patients with severe persistent asthma were randomized 2:1 to receive either daily oral masitinib (271 patients) at a dose of 6 mg/kg in addition to high-dose inhaled corticosteroids (ICS) and/or long-acting beta-agonists (LABA), or placebo (133 patients). All patients began with a 2-week placebo run-in period before receiving either the intervention or placebo for 36 weeks, with a possible extension up to 96 weeks.
Chanez and colleagues analyzed the rate of annual severe exacerbation through 36 and up to the 96-week extension, with secondary endpoints measuring forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), Asthma Control Questionnaire (ACQ and Asthma Quality of Life Questionnaire (AQLQ). The researchers also assessed a subgroup of patients with baseline eosinophil count ≥150 cells/µL. In the trial, a severe exacerbation was defined as an exacerbation that resulted in hospitalization or required maintenance corticosteroids for 3 days or more.
Overall, there were 240 patients receiving masitinib and 115 patients receiving placebo available for the primary analysis. Dr. Chanez and colleagues found patients who received masitinib in addition to their standard asthma regimen had a 35% reduction in severe exacerbations compared with patients who received placebo (rate ratio, 0.64; 95% CI, 0.48-0.84; P = .0014). In a subgroup analysis of patients with eosinophil counts ≥ 150 cells/µL, there was a 38% reduction of severe exacerbations compared with placebo (rate ratio, 0.69; 95% CI, 0.49-0.95; P = .0249).
The researchers noted 226 of 271 patients (83.4%) experienced one or more adverse events in the masitinib group compared with 109 of 133 patients (82.0%) taking placebo. In the masitinib group 48 of 271 patients (17.7%) had a serious adverse event compared with 22 of 133 patients (16.5%) in the placebo group, and 130 of 271 patients (48.0%) had a severe adverse event compared with 61 of 133 patients (45.9%) in the placebo group.