Therapeutic Potential of BTK Inhibitor Tolebrutinib in Non-Relapsing Secondary Progressive Multiple Sclerosis: Erik Wallstroem, MD, PhD

HERCULES, a phase 3 trial (NCT04411641), assesses the efficacy and safety of tolebrutinib (Sanofi), an investigational Bruton Tyrosine kinase (BTK) inhibitor, in patients with non-relapsing secondary progressive multiple sclerosis (nrSMPS), a disease for which there are limited treatment options available. This patient population was defined as those with an Expanded Disability Status Scale (EDSS) score between 3.0 and 6.5, no relapses for the previous 24 months, and documented evidence of disability accumulation in the previous 12 months.

Recently, Sanofi announced positive topline data from the trial showing that the agent met its primary end point of reducing 6-month confirmed disability progression (CDP) among treated patients. For context, 6-month CDP was defined as the increase of at least 1 point in EDSS score when baseline score was less than or equal to 5, or an increase of at least 0.5 point when the baseline EDSS score was greater than 5. While these were merely topline findings, the company is expected to present detailed results at the upcoming European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) medical meeting in Copenhagen, Denmark, September 20, 2024.

Following the announcement, NeurologyLive^® sat down with Erik Wallstroem, MD, PhD, senior vice president, global head of Neurology Development at Sanofi, to discuss the implications of the data in this difficult-to-treat population. He spoke about the mechanism of action of tolebrutinib, how it differs from other BTK inhibitors and agents in development, and why the company believes it can be successful in the long-term. Furthermore, he gave clinical insight on the reasons behind the lack of therapeutic success in treating nrSPMS.