A randomized, placebo-controlled study (AB10015, NCT02588677) previously demonstrated that masitinib (4.5 mg/kg/d), administered orally as an add-on to standard riluzole over 48 weeks, slowed the rate of functional decline in ALS patients having an ALSFRS-R progression rate from disease-onset to baseline (ΔFS) of <1.1 points/month.

Survival status of all patients originally randomized in AB10015 was collected from participating investigational sites (75 months average follow-up from diagnosis). Survival analysis (using the multivariate log-rank test and Cox proportional-hazards model, with stratification factors as covariates) was performed on the intention-to-treat population and enriched subgroups, which were defined according to initial randomization, ΔFS and baseline disease severity.

In ALS patients with mild or moderate disease severity at baseline (i.e., patients with ≥2 on each ALSFRS-R individual component) and ΔFS <1.1 points/month (i.e., exclusion of faster progressors), masitinib 4.5mg/kg/d (n=45) prolonged survival by 25 months relative to those treated with riluzole alone (n=62) (median OS of 69 versus 44 months, respectively, P=0.037) with a 47% reduced risk of death (Hazard Ratio 0.53 (95%CI[0.31–0.92]); P=0.025). Significant treatment-effect for this cohort was also observed for ΔALSFRS-R at week-48 and time-to-event analysis (PFS). Conversely, no long-term survival advantage was observed for the overall masitinib 4.5 mg/kg/d cohort of study AB10015 (regardless of baseline disease severity or ΔFS) or for the low-dose (3.0 mg/kg/d) masitinib treatment-arm.

Taken together, a consistently significant treatment effect in terms of median OS, hazard ratio of death, ∆ALSFRS-R and PFS, provides evidence that oral masitinib (4.5 mg/kg/d) can slow ALS progression, provided that patients have not suffered severe impairment of ALSFRS-related functionality at the time of treatment initiation.