Masitinib is a first-in-class tyrosine kinase inhibitor targeting the innate immune system. Results from a randomised trial with innovative design features indicated it may present a new treatment option for primary progressive MS (PPMS) and non-active secondary progressive MS (nSPMS). Masitinib showed a significant impact on the Expanded Disability Status Scale (EDSS) score in both disease groups.

The presentation of these trial results was highly anticipated because the small-molecule drug masitinib has a novel mechanism of action. It is thought to have an impact on the innate immune system via inhibition of mast cell and microglia/macrophage activity, through inhibition of c-Kit, Lyn, Fyn, and MCSFR-1 kinases. Masitinib may be applicable in a broad range of neurodegenerative diseases, including MS, ALS, and perhaps even Alzheimer’s disease. Proof-of-concept that masitinib slows progressive MS was previously demonstrated [1].

Results of a randomised (2:1), double-blinded, placebo-controlled, phase 2b/3 trial were presented [2]. The trial had novel design features, evaluating 2 independent parallel groups: 4.5 mg/kg/day versus matched placebo, and titrated 6.0 mg/kg/day versus placebo.

The study included 300 patients with either PPMS or nSPMS. Mean age was 49.3 years, median baseline EDSS score was 5.5. They received 96 weeks of masitinib (n=199) or placebo (n=101). The primary endpoint was overall EDSS change from baseline, expressed as least-squares means difference (Δ-EDSS, positive value indicates worsening). Treatment effect was expressed as between-group difference (Δ-LSM, negative value favours masitinib).

Masitinib (4.5 mg/kg/day) was significantly more effective than placebo: Δ-EDSS was 0.001 versus 0.098, respectively, and Δ-LSM -0.097 (P=0.0256). This treatment effect was numerically maintained versus placebo when stratifying the nSPMS (n=120 vs 56) and PPMS (n=79 vs 45) groups. Masitinib was associated with a significantly (39%) higher relative probability of either reduction in EDSS progression or increase in EDSS improvement (P=0.0446). Also observed were significantly lower relative risks of 42% for first progression (P=0.034), and of 37% for 12-weeks confirmed progression (P=0.159). Efficacy results from the high-dose parallel group were inconclusive and not reported in this presentation. Safety was consistent with the known profile of masitinib. In the experimental and placebo group, 94.5% and 87.1%, respectively, experienced ≥1 adverse event.


  1. Vermersch P, et al. BMC Neurol. 2012 Jun 12;12:36.
  2. Vermersch P, et al. MSVIRTUAL2020, FC04.01.