Sanofi’s tolebrutinib has been shown to delay disability progression in multiple sclerosis (MS) patients, according to phase 3 results published in the New England Journal of Medicine (NEJM).
The late-stage HERCULES trial has been evaluating the investigational oral Bruton’s tyrosine kinase (BTK) inhibitor in patients with non-relapsing secondary progressive MS (nrSPMS), where there are currently no treatment options approved.
Tolebrutinib was shown to delay the time to onset of six-month confirmed disability progression by 31% compared to placebo in nrSPMS patients.
Results from the phase 3 GEMINI 1 and 2 trials, which have been assessing the drug in relapsing forms of the neurological disorder, were also published in NEJM.
The GEMINI studies did not meet their shared primary endpoint of reducing annualised relapse rate compared to Sanofi’s current oral MS therapy Aubagio (teriflunomide), however, a pooled analysis showed that tolebrutinib delayed the time to onset of six-month confirmed disability worsening by 29% versus Aubagio.
Approximately 2.9 million people worldwide are living with MS, a chronic immune-mediated disease of the central nervous system that disrupts communication between the brain and the rest of the body.
Relapsing MS, characterised by attacks of worsening neurologic function followed by partial or complete recovery periods, accounts for about 85% of initial diagnoses, while nrSPMS, which refers to patients who have stopped experiencing relapses but continue to accumulate disability, is much less common.
Sanofi outlined that tolebrutinib has the potential to be the first therapy to modulate immunologic drivers of chronic inflammation behind the blood-brain barrier, which plays a crucial role in MS disability accumulation.
“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 MS,” said Erik Wallström, global head of neurology development at Sanofi.
Tolebrutinib was accepted for priority review by the US Food and Drug Administration (FDA) last month as a treatment for nrSPMS and to slow disability accumulation independent of relapse activity in adults.
The FDA has given the drug a target action date of 28 September 2025, and a regulatory submission dossier is currently under review in the EU.