Sanofi’s Tolebrutinib phase 3 data demonstrates benefit on disability progression in multiple sclerosis

Sanofi announces their new positive results from the HERCULES phase 3 study demonstrating that tolebrutinib delayed disability progression in people with non-relapsing secondary progressive multiple sclerosis, where there are currently no treatment options approved. These findings further support the differentiated mechanism of oral, brain-penetrant tolebrutinib, targeting disability progression independent of relapse activity.

Robert Fox, MD
Vice Chair of Research at Cleveland Clinic’s Neurological Institute, Cleveland, Ohio, US, and chair of the HERCULES global steering committee
“Tolebrutinib represents a new class of therapy for the treatment of multiple sclerosis. In this large phase 3 study, tolebrutinib was found to slow the progression of disability in a subset of multiple sclerosis for which we have no approved therapies – non-relapsing secondary progressive disease. The results of this study signal a new chapter in multiple sclerosis because we finally found a potential way to treat non-relapsing secondary progressive forms.”
Dr Fox is a paid advisor to Sanofi for the HERCULES study.

Erik Wallström, MD, PhD
Global Head of Neurology Development
“By targeting disability progression mechanisms behind the blood-brain barrier, tolebrutinib has the potential to be a practice-changing therapeutic option for people living with multiple sclerosis. The data published in NEJM support our larger commitment to the multiple sclerosis patient community, transforming the treatment paradigm to defy disability across the disease spectrum.”

Note that the HERCULES data demonstrated that tolebrutinib delayed the time to onset of 6-month confirmed disability progression by 31% compared to placebo (hazard ratio [HR] 0.69; 95% confidence interval [CI] 0.55-0.88; p=0.003).

Tolebrutinib was generally well-tolerated across all arms of the studies for all participants. In HERCULES, liver enzyme elevations were observed in 4.0% of participants receiving tolebrutinib compared with 1.6% in the placebo group. A small  proportion of participants in the tolebrutinib group experienced peak ALT increases of >20xULN, all occurring within the first 90 days of treatment. All but one case of liver enzyme elevations resolved without further medical intervention. Prior to the implementation of more frequent liver enzyme monitoring following treatment initiation, one participant in the tolebrutinib arm received a liver transplant and died due to post-operative complications. The implementation of more frequent liver monitoring may help to mitigate serious liver sequelae. Other deaths in the study were assessed as unrelated to treatment by investigators; deaths were even across the placebo and tolebrutinib arms at 0.3%.

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Related Topics and Keywords

multiple sclerosis, Sanofi, tolebrutinib, Tolebrutinib phase 3 data