Sanofi’s tolebrutinib has met the primary endpoint in the HERCULES Phase 3 clinical trial in patients with non-relapsing secondary progressive multiple sclerosis (nrSPMS).
Tolebrutinib is an investigational oral brain penetrant Bruton tyrosine kinase (BTK) inhibitor. It is being assessed in several Phase 3 clinical trials for different forms of MS.
The HERCULES trial evaluated tolebrutinib’s effectiveness and safety in nrSPMS compared to a placebo. Participants were randomised to get either daily oral tolebrutinib or a placebo for up to around 48 months.
The primary endpoint was to measure six-month confirmed disability progression (CDP) based on changes in Expanded Disability Status Scale (EDSS) scores.
According to the findings, tolebrutinib achieved the primary endpoint by significantly delaying the onset of CDP in patients with nrSPMS compared to placebo.
Preliminary liver safety results were consistent with findings from earlier studies of tolebrutinib.
Sanofi research and development head Houman Ashrafian said: “Tolebrutinib represents an unprecedented breakthrough as a potential first-in-disease treatment option with clinically meaningful benefit in disability accumulation.
“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.”
Along with HERCULES, the GEMINI 1 and GEMINI 2 studies have also assessed the BTK inhibitor. However, the GEMINI 1 and 2 Phase 3 studies of tolebrutinib did not achieve the primary endpoint of reducing the annualised relapse rate (ARR) compared to teriflunomide.
However, the analysis of a key secondary endpoint showed a considerable delay in onset, supporting the CDP data observed in the HERCULES study.
The PERSEUS Phase 3 study, which is currently ongoing, is assessing the time to onset of CDP in patients with primary progressive MS. Results from this study are expected in 2025.
In 2022, the US Food and Drug Administration (FDA) announced a partial clinical hold on Phase 3 studies of tolebrutinib based on a few cases of drug-induced liver injury.
The latest results follow Sanofi’s recent announcement of positive outcomes from a mid-stage study of its investigational CD40L monoclonal antibody, frexalimab, in relapsing MS.
