Conference Coverage

Masitinib May Provide Clinical Benefits for Patients with ALS

Patients using masitinib have reduced functional deterioration and a 25% delay in disease progression.


SAN DIEGO—Masitinib may provide meaningful clinical benefits for patients with amyotrophic lateral sclerosis (ALS), according to research presented at the 142nd Annual Meeting of the American Neurological Association. Early initiation of masitinib may be more beneficial than delayed initiation.

The worldwide prevalence of ALS is approximately 235,000. By 2040, the prevalence is expected to increase by 69%. Riluzole, the only widely available drug for the treatment of ALS, has been associated with little improvement in quality of life and modest increase in survival. IV edaravone demonstrated efficacy only in patients in good clinical condition, which is estimated to be less than 7% of patients with ALS.

Masitinib, an oral tyrosine kinase inhibitor with activity against CSF1/CSF1R signaling and mast cell function, is under investigation as a therapeutic option for patients with ALS. Masitinib provides neuroprotection in the CNS and peripheral nervous system by targeting microglia and macrophage and mast cell activity. The drug has been associated with significantly slower progression of paralysis in post paralytic rats. To test this therapy in patients with ALS, Angela Genge, MD, Director of the ALS Clinic at the Montreal Neurological Institute and Hospital, and colleagues conducted a double blind, placebo-controlled, randomized trial.


A total of 394 people from nine countries were included in the study. Patients with ALS were randomized to riluzole (100 mg/kg) plus either 4.5 mg/kg/day of oral masitinib, 3.0 mg/kg/day of oral masitinib, or placebo over 48 weeks.

The primary end point was absolute change in ALS Functional Rating Scale-Revised (ALSFRS-R) at 48 weeks in patients with baseline ALSFRS-R progression of less than 1.1 points per month. Secondary end points included the 40-item ALS Assessment Questionnaire (ALSAQ-40), forced vital capacity, and survival to event (defined as ALSFRS-R deterioration of 9 points from baseline or death). Researchers categorized participants as normal progressors (ie, those with a rate of change in ALSFRS-R score < 1.1 points per month) or faster progressors (ie, those with a rate of change in ALSFRS-R score ≥ 1.1 points per month).

Masitinib showed significant benefit over placebo in ALSFRS-R. At week 48, the score had decreased by 12.6 points among controls, compared with 9.2 points in the masitinib groups. Masitinib was associated with 27% slowing of ALSFRS-R deterioration, 29% slowing of deterioration in quality of life, 22% slowing of deterioration in respiratory function, and 25% delay in disease progression.

Secondary analyses also indicated masitinib’s superiority to placebo. A post hoc analysis indicated that early treatment (ie, at less than 24 months duration of illness) conferred greater benefits than delayed treatment.

Adverse events with greatest positive difference between masitinib and placebo treatment-arms were maculopapular rash and peripheral edema. The rate of adverse events was 78.9% for placebo, 88.4% for the 4.5-mg/kg/day dose of masitinib, and 84.7% for the 3.0-mg/kg/day dose of masitinib. No deaths related to study treatment were reported in either masitinib or placebo groups. Patients who had milder symptoms or shorter duration of illness showed enhanced masitinib treatment effect.



Erica Tricarico

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