The severity of asthma can be graded from mild intermittent disease, with little impact on everyday life, through to severe disease with permanent symptoms and serious limitation of normal activities.
Data suggests that mast cells are involved in allergic and anaphylactic reactions, playing an important role in hypersensitivity and inflammatory processes of the disease and also tissue remodeling of the airways.
Masitinib is currently investigated both in severe asthma uncontrolled by oral corticosteroids (OCS) and severe asthma uncontrolled by high dose inhaled corticosteroids (ICS).
Asthma uncontrolled by oral corticosteroid is the most severe form of asthma (step 5 of the GINA guidelines for asthma management) and represents a high unmet medical need. Quality-of-life for such patients is severely affected, with major reduction in lung function, restrictions on activities of daily living, frequent asthma exacerbations and greater risk of life-threatening asthma exacerbations.
Summary of severe asthma clinical program with masitinib
|Phase||Design||Population||Primary Target||Patient Target||IDMC recommandation||Study Status||Related publications|
|2a||Double-blind, placebo-controlled, parallel-group study||Patients with severe corticosteroid dependent asthma||
Change from baseline in corticosteroids doses, after
4 months of treatment
|44||NA||Study completed||Humbert, 2009|
|2/3||Prospective, double-blind, placebo-controlled, 2-parallel groups study||Patients with severe asthma uncontrolled with oral corticosteroids||Severe Asthma exacerbation rate adjusted on the available person-time (time to end of treatment)||420||Continuation of the study without resampling option (based on interim analysis and safety data)||Recruitment completed||–|
|3||Prospective, double-blind, placebo-controlled, 2-parallel groups study||Patients with severe asthma uncontrolled with high dose of inhaled corticosteroids and with elevated eosinophil levels||Severe Asthma exacerbation rate adjusted on the available person-time (time to end of treatment)||350||Continuation of the study (based on safety data)||Recruitment completed|
Phase 2a proof of concept
Clinical phase 2a proof of concept with masitinib in asthma supported the development of masitinib in severe asthma uncontrolled with corticosteroids. In this phase 2a study, a comparable reduction in oral corticosteroids was achieved with masitinib and placebo at 16 weeks of treatment (median reduction of 78% and 57% in the masitinib and placebo arms, respectively). However, when focusing on the truly dependent corticosteroids asthma patients, meaning patients receiving > 15mg equivalent prednisone per day, a significant difference was observed. In this subgroup of patients, doses of corticosteroids were reduced by 52% in masitinib treated patients compared to 28% in placebo treated patients. In parallel, the number of patients experiencing at least one exacerbation during the study period was 42.4% and 54.5% in the masitinib-treated and placebo groups, respectively. Additionally, an improved asthma control was observed in masitinib- treated patients, the Asthma Control Questionnaire score was significantly better in the masitinib arm as compared to placebo with a reduction by 0.99 unit at week 16 vs 0.43 unit in the placebo arm.
Phase 3 studies
First phase 3 study
Second phase 3 study
Humbert M, de Blay F, Garcia G, Prud’homme A, Leroyer C, Magnan A, Tunon-de-Lara JM, Pison C, Aubier M, Charpin D, Vachier I, Purohit A, Gineste P, Bader T, Moussy A, Hermine O, Chanez P.
Allergy. 2009 Aug;64(8):1194-201. doi: 10.1111/j.1398-9995.2009.02122.x.
The tyrosine kinase inhibitor masitinib blunts airway inflammation and improves associated lung mechanics in a feline model of chronic allergic asthma.
Lee-Fowler TM, Guntur V, Dodam J, Cohn LA, DeClue AE, Reinero CR. Int Arch Allergy Immunol. 2012;158(4):369-74.