AB Science SA summarized the presentation that was made on masitinib in amyotrophic lateral sclerosis (ALS) at the American Academy of Neurology(AAN) 2023 Annual Meeting in Boston, USA (April 22-27, 2023). The title of this presentation is Masitinib Shows Prolonged Survival in Amyotrophic Lateral Sclerosis (ALS) Patients with Mild or Moderate Disease Severity at Baseline. The new analysis that was presented was performed in ALS patients prior to any complete loss of physical function (corresponding to a score of 0 on any ALSFRS-R individual component and regardless of baseline progression rate), which encompassed about 80% of the overall AB10015 study population.

It is clinically relevant to analyze this population as patients with very severe ALS (i.e. with ALSFRS-R score of zero on any ALSFRS-R individual component) are unable to perform certain physical functions and in the context of treating neurodegenerative disease, any improvement in these lost functions is beyond what can be reasonably expected from an interventional drug, no matter how effective it may be in preventing further disease progression. The exclusion of these very severe patients is also consistent with the proposed mechanism of action of masitinib on microglia and mast cell activity to slow progression rather than as a cure for ALS. Based on this mechanism of action, it would be inappropriate to target those in the last stages of their disease.

Results in these patients prior to any complete loss of physical function showed a statistically significant 18.4% relative benefit on CAFS endpoint in favor of masitinib 4.5 mg/kg/day as compared with control (p=0.035). The composite endpoint of functioning and survival (CAFS) was not a recommended primary endpoint when study AB10015 was designed. However, since completion of study AB10015, the CAFS has become increasingly requested as a primary endpoint to determine efficacy in ALS trials, by FDA and Health Canada in particular.

This new result therefore represent a key analysis for study AB10015. The positive treatment-effect in CAFS was supported by converging results on change in ALSFRS-R score at week 48 (+25% difference, p=0,027), respiratory function at week 48 (+20.4% difference, p=0,022) and quality of life at week 48 (19.8% difference, p=0,025). In addition, with long-term survival follow-up (median follow-up of 75 months), there was a close significant median overall survival benefit of +8 months in favour of masitinib 4.5 mg/kg/day (46 [ 30; 69 ] vs 38 [ 29; 49 ], p-value=0.0684).

Furthermore, patients with moderate disease only (i.e. those patients having ALSFRS-R score greater than 1 on any ALSFRS-R individual component and no fast disease progression) showed even better survival, prolonged of 25 months with masitinib, with a reduced risk of death of 44% (P<0.05). As a reminder, the development program of masitinib in ALS comprises a 48-week clinical trial (AB10015), including long-term survival follow-up analysis, and an on-going confirmatory phase 3 trial (AB19001).