Masitinib Significantly Reduced Exacerbations in Uncontrolled Severe Asthma

After careful consideration, the American Thoracic Society canceled its annual meeting that was to take place in Philadelphia, Pennsylvania from May 15-20, because of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Although the live events will not proceed as planned, our readers can still find coverage of research that was scheduled to be presented at the meeting. A virtual event is being planned for later this year.

The first-in-class tyrosine kinase inhibitor masitinib decreased asthma exacerbations greater than placebo in patients with severe asthma uncontrolled by oral corticosteroids, according findings intended to be presented at the American Thoracic Society International Conference. (Select research is slated to be presented in a virtual format later this year.)

Patients with severe persistent asthma that was uncontrolled by oral corticosteroids >5 mg/d and high-dose inhaled corticosteroids/ long-acting beta agonists were randomly assigned to either masitinib (n=240) or placebo (n=115). The 36-week treatment phase was initiated after a 2-week single-blind placebo run-in period.

The primary end point of the AB07015 study (ClinicalTrials.gov Identifier: NCT01449162) was the reduction in the annualized severe asthma exacerbation rate for overall exposure. A severe exacerbation event was defined as worsening asthma causing hospitalization or an increase from stable corticosteroid maintenance dose for ≥3 days. Key secondary end points included forced expiratory volume in 1 second (FEV₁), forced vital capacity, asthma control questionnaire, and asthma quality of life score. In addition to the primary analysis cohort, a safety population that included 271 patients randomly assigned to masitinib and 133 patients randomly assigned to placebo was also enrolled.

Across treatment groups, the average exposure time was approximately 60 weeks. Compared with placebo, treatment with masitinib was associated with a significantly reduced severe asthma exacerbation rate of 35% (rate ratio [RR], 0.64; 95% CI, 0.48-0.84; P =.0014). In a subpopulation of patients with an eosinophil count of ≥150 cells/μL, there was a significant reduction in severe exacerbations of 38% in patients who were treated with masitinib compared with placebo (RR, 0.69; 95% CI, 0.49-0.95; P =.0249). At week 96, patients treated with masitinib had a greater least-squares mean change from baseline in FEV₁ compared with placebo (0.0989 vs 0.0314, respectively; RR, 0.0675; 95% CI, 0.0125-0.1225; P =.016).

The proportions of patients who presented with ≥1 adverse event were 83.4% for masitinib vs 82.0% for placebo in the safety population. The rates of serious adverse events were 17.7% and 16.5% for masitinib and placebo, respectively. Additionally, severe adverse events occurred in 48.0% of patients treated with masitinib compared with 45.9% of patients treated with placebo.

The investigators concluded that 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.”

Reference

Chanez P, Israel E, Davidescu L, et al. Masitinib significantly decreases the rate of asthma exacerbations in patients with severe asthma uncontrolled by oral corticosteroids: a phase 3 multicenter study. Am J Respir Crit Care Med. 2020;201:A4210.

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This article originally appeared on Pulmonology Advisor