Tolebrutinib delays onset of MS disability progression in phase 3 trial

An oral brain-penetrant therapeutic delayed the onset of confirmed disability progression compared with placebo in those with non-relapsing secondary progressive MS, according to results from a phase 3 study.

The HERCULES study was a randomized, double-blind clinical trial that evaluated safety and efficacy of tolebrutinib (Sanofi) — a Bruton’s tyrosine kinase inhibitor — in patients with non-relapsing secondary progressive MS compared with placebo, Sanofi said in a press release.

Participants were randomly assigned 1:1 to receive either an oral daily dose of tolebrutinib or matching placebo for up to 48 months. The primary endpoint was 6-month confirmed disability progression (CDP), which researchers defined as a one point or greater increase in the baseline Expanded Disability Status Scale (EDSS) score when the baseline score was at least five, or an increase of at least half a point when the baseline EDSS score was less than five.

Results from HERCULES are in contrast to those of the phase 3 GEMINI 1 and 2 clinical trials, in which tolebrutinib failed to meet the primary endpoint of reducing annualized relapse rate, compared with teriflunomide, in a similar patient population. However, analysis of the secondary endpoint in the GEMINI trials of pooled 6-month data concerning confirmed disability worsening showed that treatment with tolebrutinib demonstrated a noticeable delay in the onset of such, supporting data found in HERCULES, according to Sanofi.

“Addressing disability accumulation, thought to be driven by smoldering neuroinflammation, remains the greatest unmet medical need in people with non-relapsing secondary progressive MS today,” Houman Ashrafian, MD, PhD, head of research and development at Sanofi, said in the release.

The company said that full data sets for HERCULES as well as GEMINI 1 and 2 are expected to be presented at the European Committee for Treatment and Research in Multiple Sclerosis, or ECTRIMS, later this month.