Sanofi Prepares for Regulatory Submission of Tolebrutinib in Non-Relapsing Secondary Progressive Multiple Sclerosis

Clinical Trial Outcomes:

HERCULES Study:
Tolebrutinib, Sanofi’s oral brain-penetrant BTK inhibitor, met the primary endpoint in the Phase III HERCULES study by delaying the time to onset of confirmed disability progression in patients with non-relapsing secondary progressive multiple sclerosis (nrSPMS).

GEMINI 1 and 2 Studies:
Tolebrutinib failed to meet the primary efficacy endpoints in the Phase III GEMINI 1 and GEMINI 2 studies, which evaluated its effectiveness in reducing annualized relapse rates in patients with relapsing multiple sclerosis (RMS).

Regulatory Plans:

Sanofi plans to file for regulatory approval of tolebrutinib in nrSPMS “as soon as possible” based on the positive results from the HERCULES study.

Mechanism of Action:

Tolebrutinib is an orally available and brain-penetrant inhibitor of the BTK protein, which plays a central role in the development of antibody-producing B cells and disease-driving microglia.

Safety Profile:

Preliminary analysis of liver safety in the HERCULES study showed that tolebrutinib’s liver safety profile was consistent with previous studies, with a slight increase in liver enzyme elevations observed in tolebrutinib-treated patients.

Unmet Medical Need:

The accumulation of disabilities in patients with nrSPMS remains a significant unmet medical need, and tolebrutinib represents a potential first-in-disease treatment option with clinically meaningful benefit in disability accumulation.