Drug delays SPMS disability progression in clinical trial

A new phase 3 clinical trial has found that tolebrutinib significantly delays disability progression in patients with secondary progressive multiple sclerosis (SPMS).

Tolebrutinib is an investigational drug under development for the treatment of MS. It is a Bruton’s tyrosine kinase (BTK) inhibitor, meaning it targets an enzyme involved in the activation of B cells and microglia, which are immune cells that play a role in MS.

The trial included 1,131 adults living with nonrelapsing SPMS, meaning they had not experienced a relapse in the past two years but continued to show gradual worsening of disability.

Over a median follow-up period of about two and a half years, participants who received tolebrutinib experienced a 31% reduction in the risk of six-month confirmed disability progression compared to those given a placebo. Additionally, those on the drug were 88% more likely to show confirmed improvement in disability over six months. MRI scans also revealed a 38% reduction in the number of new or enlarging brain lesions among patients taking tolebrutinib.

While these results are encouraging for progressive MS, tolebrutinib did not perform as well in trials for relapsing MS. In the GEMINI 1 and 2 studies, which compared it to the approved drug Aubagio (teriflunomide), tolebrutinib failed to demonstrate superior efficacy in reducing relapse rates.

Concerns about safety also remain. Roughly 5% of patients in the HERCULES trial developed elevated liver enzymes — a known issue with BTK inhibitors. One patient required a liver transplant and later died due to complications. In response, Sanofi has strengthened its liver monitoring protocols in all ongoing and future trials involving tolebrutinib.

The drug’s manufacturer Sanofi has submitted a request to the U.S. Food and Drug Administration (FDA) for approval of tolebrutinib for use in nonrelapsing SPMS. A regulatory decision is expected by September 28, 2025.