Masitinib Appears Promising for Slowing Disability Worsening in Progressive MS

Masitinib 4.5 mg/kg/d eased disability progression in patients with primary progressive multiple sclerosis (MS) and nonactive secondary progressive MS, according to results from a phase 3, randomized clinical trial funded published online in Neurology: Neuroimmunology & Neuroinflammation. The study was funded by drug manufacturer AB Science.

“Masitinib at 4.5 mg/kg/d can benefit patients by slowing EDSS-based disability worsening; however, validation of these findings via a confirmatory phase 3 study will be necessary, in part because neuroimaging data were not collected during the current study and also due to an absence of signal on secondary end points,” the authors wrote.

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The double-blind, two parallel-group, placebo-controlled trial included 611 patients at 116 hospital clinics and specialized MS centers in 20 countries. Some 301 patients were randomly assigned to receive masitinib 4.5 mg/kg/d—a selective tyrosine kinase inhibitor—or placebo. In a second parallel group, 310 patients were randomly assigned masitinib at an initial dose of 4.5 mg/kg/d for 12 weeks, then titrated to a dose of 6.0 mg/kg/d or placebo. For both groups, the treatment period lasted 96 weeks.

At the 4.5 mg/kg/d dose, masitinib showed significant benefit over placebo as measured by change from baseline on the Expanded Disability Status Scale (EDSS). According to the study, the overall EDSS score progressed 0.001 in the masitinib group compared with 0.098 in the placebo group, with the -0.097 between-group difference in favor of masitinib. No elevated risk of infection occurred in the masitinib group, and safety findings were consistent with the medication’s known profile (diarrhea, nausea, rash, and hematologic events).

Findings from the uptitrated masitinib 6.0 mg/kg/d parallel group were inconclusive regarding efficacy, researchers reported. No new safety signals occurred.

 “Overall, study AB07002 represents the first successful randomized, controlled, phase 3 trial in progressive MS of a tyrosine kinase inhibitor, targeting innate immune cells,” authors concluded.

Reference

Vermersch P, Brieva-Ruiz L, Fox RJ, et al. Efficacy and safety of masitinib in progressive forms of multiple sclerosis: a randomized, phase 3, clinical trial. Neurol Neuroimmunol Neuroinflamm. Published online February 21, 2022. doi:10.1212/NXI.0000000000001148