AB Science updates on masitinib development for progressive multiple sclerosis after ECTRIMS 2024

AB Science has provided an important update on the development of its drug, masitinib, for treating progressive forms of multiple sclerosis (MS). This update follows the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) 2024 conference in Paris.

The development of masitinib for progressive MS is based on the MAXIMS study (AB20009), a randomized, double-blind, phase 3 trial. This study focuses on patients with primary progressive multiple sclerosis (PPMS) and non-active secondary progressive multiple sclerosis (nSPMS). Participants must have an Expanded Disability Status Scale (EDSS) score between 3.0 to 6.0, documented disease progression over the past two years, and no T1 Gadolinium-enhancing brain lesions. The study's primary goal is to assess the effect of masitinib on the time to confirmed disability progression.

Recent findings on tolebrutinib, presented at the ECTRIMS 2024 conference, have reinforced the idea that targeting microglia in nSPMS is a valid therapeutic approach. Tolebrutinib acts on microglia through the Bruton Tyrosine Kinase (BTK) enzyme. Similarly, masitinib targets microglia but via a different enzyme, M-CSFR1 (Macrophage Colony Stimulating Factor Receptor-1), and has shown positive phase 2B results (AB07002) that align with tolebrutinib data.

In terms of effectiveness, masitinib demonstrated a 37% reduction in EDSS progression confirmed at three months in study AB07002, compared to 23% with tolebrutinib in the Hercules study. At six months, masitinib reduced EDSS progression by 32%, while tolebrutinib achieved a 31% reduction. Moreover, masitinib significantly improved manual dexterity as measured by the 9-hole Peg test.

Masitinib has also shown potential in decreasing serum neurofilament light chain (NfL) concentration, which may indicate reduced neuronal damage. Beyond targeting microglia, masitinib also affects mast cells, which play a significant role in progressive MS and have been highlighted in various studies focusing on the experimental autoimmune encephalomyelitis (EAE) model of MS.

Safety data for masitinib are robust, with long-term exposure documented across multiple indications. Approximately 2,200 patients have received at least one dose of masitinib, over 1,300 patients have taken it for more than six months, and nearly 1,000 have been treated for over a year. Contrastingly, BTK inhibitors are associated with increased risks of liver injury, hypertension, and infections, suggesting there is room for alternative treatments.

In conclusion, masitinib is positioned as a promising alternative to BTK inhibitors in the development of new drugs for both primary and non-active secondary progressive MS. Professor Patrick Vermersch, the principal investigator of the MAXIMS study, emphasized the significance of tolebrutinib data and the potential of masitinib as a credible alternative for treating progressive forms of MS. He also highlighted the importance of considering mast cells in MS treatment strategies.

The recent advancements in masitinib development align with AB Science's strategic direction, strengthening the scientific rationale for its use in progressive MS. The results from the phase 2B/3 study (AB07002) support its potential efficacy, showing a statistically significant reduction in cumulative EDSS change and a substantial decrease in the risk of disability progression.

AB Science, founded in 2001, specializes in the research, development, and commercialization of protein kinase inhibitors (PKIs). Their lead compound, masitinib, has applications in veterinary medicine and is under development for human use in oncology, neurological diseases, inflammatory diseases, and viral diseases. The company is headquartered in Paris, France, and is listed on Euronext Paris.