Masitinib significantly reduced asthma exacerbations in patients with severe asthma uncontrolled by oral corticosteroids compared with placebo treatment, according to new data.
Masitinib (AB Science) is a first-in-class small tyrosine kinase inhibitor that targets mast cell activity.
Researchers conducted a randomized, double-blind, placebo-controlled, phase 3, multicenter study to assess oral masitinib (6 mg/kg per day) for treatment of severe asthma uncontrolled by oral corticosteroids (> 5 mg per day) and high-dose inhaled corticosteroids/long-acting beta agonists. The researchers also evaluated outcomes in a predefined subgroup of patients with an eosinophil count of 150 cells/L or more.
The primary endpoint was reduction of annual asthma exacerbation rate; a severe asthmatic event was defined as worsening asthma leading to an increase in corticosteroid dose for 3 or more days or hospitalization. Safety was assessed in those receiving at least one dose of masitinib, including in those receiving low-dose (5 mg or less per day) oral corticosteroids.
The primary analysis included 355 patients (240 assigned masitinib; 115 assigned placebo) and the safety population included 404 patients (271 assigned masitinib; 133 assigned placebo).
Treatment protocol was a 2-week single-blind, placebo run-in period, followed by masitinib treatment for 36 weeks, with possible blinded extension until at least 96 weeks, according to the abstract. Average exposure time to masitinib was about 60 weeks and was well balanced across the treatment and placebo groups, according to the abstract.
Results published in the American Journal of Respiratory and Critical Care Medicine showed masitinib significantly reduced severe asthma exacerbations by 35% compared with placebo (rate ratio = 0.64; 95% CI, 0.48-0.84; P =.0014). Masitinib reduced severe exacerbations by 38% compared with placebo (rate ratio = 0.69; 95% CI, 0.49-0.95; P=.0249) in the predefined subgroup of patients with eosinophil count of 150 cells/L or more. The researchers also reported improvements with masitinib in secondary endpoints including forced expiratory volume in 1 second, forced vital capacity, asthma control and asthma quality of life scores.
Of the 271 patients in the safety population assigned masitinib, 83.4% had at least one adverse event compared with 82% in the placebo group. The masitinib and placebo groups also had similar rates of serious adverse events (17.7% vs. 16.5%, respectively) and severe adverse events (48% vs. 45.9%, respectively).
“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,” Pascal Chanez, MD, PhD, of Aix Marseille University in Provence, France, and colleagues wrote in the abstract.
The data were scheduled for presentation at the American Thoracic Society International Conference.
- Chanez P, et al. B93. Late Breaking Clinical Trials in Airway Diseases: 2020. Presented at: American Thoracic Society International Conference (virtual).