Efficacy and safety of masitinib in amyotrophic lateral sclerosis patients prior to loss of functionality: A subgroup analysis optimizing the benefit-risk profile of masitinib

作者：Albert C. Ludolph, Jesús S. Mora, Patrick Vermersch, Alain Moussy, Colin D. Mansfield, Olivier Hermine · 发表于：medRxiv · 年份：2025 · DOI：10.64898/2025.12.08.25341479 · 被引用次数：1 · 研究领域：Amyotrophic Lateral Sclerosis Research、Spondyloarthritis Studies and Treatments、Peripheral Neuropathies and Disorders

Abstract Background Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that urgently requires new treatments. Masitinib, a tyrosine kinase inhibitor targeting microglia and mast cells, aims to slow disease progression by reducing neuroinflammation. A previously reported phase 2b/3 study showed that masitinib (4.5 mg/kg/day) with riluzole significantly slowed decline of the revised amyotrophic lateral sclerosis functional rating scale (ALSFRS-R) over 48 weeks in a specific patient population. However, a baseline imbalance was noted, with a higher proportion of patients with very severe loss of functionality (those with a score of 0 on at least one item of the ALSFRS-R) in the masitinib group. This post-hoc analysis evaluated the efficacy and safety of masitinib in the subgroup ‘ALS prior to any complete loss of functionality’ to eliminate potential bias and evaluate the effect of treatment in the early phase of the disease. Methods Data from study AB10015 were analyzed for patients with a score of at least 1 on all ALSFRS-R items at baseline. The primary endpoint was the change in ALSFRS-R score (ΔALSFRS-R) at week 48. Secondary endpoints included progression-free survival (PFS) and overall survival (OS). Results In the subgroup (N=84 for masitinib, N=104 for placebo), masitinib demonstrated an increase of the treatment effect compared with that in the primary analysis population. The ΔALSFRS-R difference between masitinib and placebo was 4.04 points (p=0.0065)...