Treatment drug results in a significant reduction in severe exacerbations for patients with eosinophil ≥150 cells/µL.
Pascal Chanez, MD, PhD
New data points to masitinib as a promising treatment in reducing asthma exacerbation in patients with severe asthma that are uncontrolled by oral corticosteroids.
A team, led by Pascal Chanez, MD, PhD, Aix Marseille University, planned to present the data on the evaluation of oral masitinib (6 mg/kg/day) treatment of severe persistent asthma remaining uncontrolled by oral corticosteroid (OCS) (>5mg/day) and high-dose ICS/LABA at the American Thoracic Society (ATS) 2020 International Conference.
Masitinib is a small molecule drug that targets KIT, LYN, and FYN—3 kinases involved in the function of dendritic, epithelial, and mast cells. These cells are implicated in various mechanisms of asthma pathogenesis.
In the past, researchers proved in a proof-of-concept trial that the treatment could improve control of steroid-dependent asthma.
In the study, each patient underwent a two-week single-blind placebo run-in period, followed by a 36-week treatment period with the possibility of a 96-week blinded extension.
The primary analysis population included 240 patients who received the study drug and 115 who received placebo, as well as 271 masitinib and 133 placebo patients who were part of the safety population.
The investigators sought a primary endpoint of the reduction of annualized severe asthma exacerbation rate for overall exposure, including the extension period, with a severe exacerbation event defined as worsening asthma leading to an increase from stable maintenance dose of corticosteroids for ≥3 days or hospitalization.
They also conducted a predefined subgroup analysis to assess patients with initial eosinophil count of ≥150 cells/µL. The team also sought secondary endpoints, including FEV1, FVC, AQC and AQLQ.
They also assessed safety in patients that received at least 1 dose of masitinib, including those receiving low-dose (≤5mg/day) OCS who were excluded from the primary analysis following a protocol amendment.
Baseline characteristics and average exposure times were balanced across all treatment arms.
The investigators found that masitinib significantly reduced severe asthma exacerbation rates by 35% when compared with placebo (RR, 0.64; 95% CI, 0.48-0.84; P = 0.0014). The treatment effect was corroborated by sensitivity analyses, including the Full Analysis Set population (n = 402). They also met secondary endpoints of the reduction in moderate or severe asthma exacerbation rates and changes from baseline to week 96 in pulmonary function and asthma control.
There was also a substantial reduction in severe exacerbations of 38% (RR, 0.69; 95% CI, 0.49-0.95; P = 0.0269) patients with the eosinophil ≥150 cells/µL subpopulation.
On the other hand, 83.4% (n = 226) of patients presented at least 1 adverse events in the masitinib group, compared to 82.0% (n = 109) for the placebo group.
The rates of serious and severe adverse events were 17.7% (n = 48) and 48.0% (n = 130) in the treatment group and 16.5% (n = 22) and 45.9% (n = 109) in the placebo group.
“Masitinib, a first-in-class tyrosine kinase inhibitor targeting mast cell activity in severe asthma patients, 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,” the authors wrote.
The study, “Masitinib Significantly Decreases the Rate of Asthma Exacerbations in Patients with Severe Asthma Uncontrolled by Oral Corticosteroids: A Phase 3 Multicenter Study,” was published online by the ATS International Conference.