Sanofi's Tolebrutinib Delays Disability Progression in Phase 3 Multiple Sclerosis Study

PARIS – Sanofi has reported positive outcomes from the Phase 3 HERCULES study evaluating its investigational drug, tolebrutinib. The study demonstrated that tolebrutinib delayed the time to onset of 6-month confirmed disability progression (CDP) by 31% in patients with non-relapsing secondary progressive multiple sclerosis (nrSPMS) when compared to placebo.

The findings were presented at the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) 2024 congress. Further analysis indicated that the number of participants experiencing confirmed disability improvement nearly doubled, with 10% in the tolebrutinib group showing improvement versus 5% in the placebo group. Sanofi intends to begin global regulatory submissions in the latter half of 2024.

While the study showed efficacy, it also noted some adverse events. Elevations in liver enzymes (greater than 3x upper limit of normal) occurred in 4.1% of participants on tolebrutinib compared to 1.6% on placebo. One participant experienced a severe liver event requiring a transplant and subsequently died from post-operative complications, prior to enhanced monitoring protocols being implemented. Most liver enzyme elevations resolved without intervention. Deaths unrelated to treatment were evenly distributed between arms.

Tolebrutinib is a brain-penetrant Bruton's tyrosine kinase (BTK) inhibitor designed to target the underlying drivers of MS progression. Sanofi highlighted the significant unmet need for treatments for secondary progressive MS and anticipates these results will support regulatory review. The company is also awaiting results for tolebrutinib investigational use in primary progressive MS, expected next year.