Tolebrutinib slows disability accumulation in secondary progressive multiple sclerosis
Key takeaways:
- Tolebrutinib was associated with a 31% reduced risk for 6-month confirmed disability progression vs. placebo.
- The percentage of serious adverse events was greater for tolebrutinib vs. placebo.
SAN DIEGO — Treatment with tolebrutinib led to greater confirmed disability improvement at 6 months compared with placebo in patients with non-relapsing secondary progressive multiple sclerosis, according to research presented at AAN.
“For over 30 years, the story of therapies in multiple sclerosis has been one of the haves and the have-nots,” Robert J. Fox, MD, staff neurologist at the Mellen Center for Multiple Sclerosis at the Cleveland Clinic, said during AAN’s Top Science Press Conference. “No therapies have been approved for secondary progressive MS without relapses ... so treatments for this form of MS represents a major unmet need.”
Fox and colleagues examined the safety and efficacy of the oral, brain-penetrant Bruton’s tyrosine kinase inhibitor tolebrutinib (Sanofi) compared with placebo for patients with non-relapsing secondary progressive MS (nrSPMS) enrolled in the global, double-blind, phase 3 HERCULES clinical trial.
Their study included 1,131 patients aged 18 to 60 years with a confirmed SPMS diagnosis, scores on the Expanded Disability Status Scale (EDSS) between 3 and 6.5, documented evidence of disability progression in the 12 months prior to enrollment and no clinical relapses during the 24 months before screening.
Participants were randomly assigned on a 2:1 basis to receive once daily 60 mg oral tolebrutinib (n = 754) or matching placebo (n = 377).
The primary outcome was progression of disability sustained for 6 months or longer, while secondary endpoints included additional disability outcomes and safety indications.
According to the results, tolebrutinib was associated with a 31% slowing of disability progression at 6 months, compared with placebo.
Data further showed that more participants experienced 6-month confirmed disability improvement with tolebrutinib vs. placebo.
Fox reported a higher rate of serious adverse events for those given tolebrutinib vs. placebo, including respiratory infections and high liver enzyme increases, which were logged within 90 days of treatment initiation.
Approximately 77% of enrollees in each group completed the trial, Fox said.
“Treatment with tolebrutinib slows the progression of disability in non-relapsing secondary progressive MS,” Fox told Healio. “This is the first time we have identified a treatment that is effective for this form of MS.”
For more information:
Robert J. Fox, MD, can be reached at neurology@healio.com.
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Fox RJ, et al. Tolebrutinib versus placebo in non-relapsing secondary progressive multiple sclerosis:
Efficacy and safety results from the phase 3 HERCULES trial. Presented at: American Academy of Neurology Annual Meeting; April 5-9, 2025; San Diego.
