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Masitinib: a first-in-class TKI as treatment of progressive MS

MS Virtual 2020
Results of a randomised phase 3 trial indicate that masitinib may be a new treatment option for both primary progressive MS and non-active secondary progressive MS [1]. Treatment with this tyrosine kinase inhibitor (TKI) resulted in a significant and sustained change in EDSS score over 2 years.

Masitinib has a novel mechanism of action which is thought to have an impact on the innate immune system by selectively inhibiting mast cell activity (measured by c-KIT, LYN, and FYN) and microglia activity (measured by CSF1R).

Results of a randomised, double-blind, placebo-controlled, phase 2b/3 trial were presented. 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. Efficacy results from the high-dose parallel group were inconclusive and not reported. The study of masitinib 4.5 mg/kg/day included 300 patients with either primary progressive MS or non-active secondary progressive MS. Mean age was 49.3 years, median baseline EDSS score 5.5. Patients received masitinib (n=199) or placebo (n=101) for 96 weeks. The primary endpoint was overall mean absolute EDSS change from baseline.

Masitinib was significantly more effective than placebo: EDSS change was 0.001 versus 0.098 (P=0.0256: see Figure). This treatment effect was numerically maintained when stratifying the non-active secondary progressive (n=120 vs 56) and primary progressive MS (n=79 vs 45) groups. Sensitivity analysis showed that masitinib was associated with a significant 39% increase in the probability of either reduction in EDSS progression or increase in EDSS improvement (P=0.0446). There was also a significant 42% lower relative risk of first progression (P=0.034) and a 37% lower relative risk of 12-weeks confirmed progression (P=0.159). Masitinib treatment effects were irrespective of baseline inflammatory status. Safety was consistent with the known profile of masitinib. In the experimental and placebo-group respectively, 94.5% and 87.1% experienced ≥1 adverse event.

Figure: Absolute changes from baseline in EDSS measured every 12 weeks up to week 96 [1]

  1. Vermersch P, et al. Masitinib in primary progressive (PPMS) and non-active secondary progressive (nSPMS) multiple sclerosis: Results from phase 3 study AB07002. MSVirtual 2020, FC04.01.


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