First-in-class tyrosine kinase inhibitor shows promise in severe asthma

A recent phase 3 study suggests that masitinib could be a novel treatment for patients with severe asthma as it demonstrated a positive benefit/risk ratio regardless of initial eosinophils level [1].

The multicentre, prospective, randomised, placebo-controlled phase 3 trial assessed masitinib 6 mg/kg/day in adult patients with severe asthma and insufficient disease control under oral corticosteroids (OCS) at >5 mg/day. The small molecule masitinib is a selective tyrosine kinase inhibitor that targets mast cell activity and exerts inhibition on platelet-derived growth factor receptor signalling associated with airway remodelling.

The study included 355 participants for the primary analysis and 404 participants for the safety evaluation. They were randomised 2:1 to receive masitinib or placebo. All participants had a baseline FEV₁ value ≥35% and <80% and at least 2 exacerbations in the previous year as well as signs of uncontrolled asthma 2 weeks before the study. The primary endpoint was defined as reduction of annualised severe asthma exacerbation rate (SAER) that included a deterioration demanding dose escalation of OCS for at least 3 days or hospitalisation. After a placebo run-in interval of 2 weeks, participants received treatment over 36 weeks, which could be followed by a blinded extension until at least week 96. This led to an average exposure time of about 60 weeks.

Compared with placebo, the rate of SAER was significantly reduced by 35% in patients on masitinib (P=0.0103; rate ratio 0.65; 95% CI 0.47-0.90). The result was supported by a sensitivity analysis of the full analysis set population. A pre-specified subgroup analysis of patients with an eosinophil level of ≥150 cells/µL showed a decrease of 38% (P=0.0156; rate ratio 0.62; 95% CI 0.42-0.91). In terms of safety, at least 1 adverse event occurred in 83.4% of the masitinib and 82% of the placebo groups. Corresponding rates for severe and serious adverse events were 48.0% vs 45.9% and 17.7% vs 16.5%, respectively. In conclusion, the investigators saw a possible new treatment option with masitinib for patients with severe asthma who are not eligible for biologic treatment.

 

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   1. Chanez P, et al. Masitinib significantly decreases the rate of asthma exacerbations in patients with severe asthma uncontrolled by oral corticosteroids: A phase 3 multicenter study. LBA B93, ATS 2020 Virtual, 5-10 Aug.

Posted on 29 October 202023 February 2021