Tolebrutinib for multiple sclerosis

Last updated Jan. 5, 2026, by Marisa Wexler, MS
Fact-checked by Inês Martins, PhD

What is tolebrutinib for MS?

Tolebrutinib is an oral therapy being developed by Sanofi to treat both relapsing and progressive forms of multiple sclerosis (MS).

Taken daily in the form of oral capsules, tolebrutinib has been shown in clinical trials to slow disability progression in nonrelapsing secondary progressive MS (SPMS) and to delay disability worsening in people with relapsing forms of MS.

Based on those findings, the therapy has been approved in the United Arab Emirates for treating nonrelapsing SPMS and slowing disability accumulation independent of relapse activity in adults with MS. Sanofi also sought U.S. approval of tolebrutinib for those indications, but the U.S. Food and Drug Administration (FDA) declined to approve it in late 2025. The therapy is also being considered for approval in Europe.

Tolebrutinib works by blocking the activity of Bruton tyrosine kinase (BTK), an enzyme that plays a key role in the inflammatory activation of several types of immune cells, including B-cells and microglia. While most available disease-modifying therapies for MS target immune processes involved in relapses, tolebrutinib is believed to target the smoldering inflammation that contributes to disability progression in the absence of relapses.

Therapy Snapshot

How will tolebrutinib be administered in MS?

Tolebrutinib is an oral medication available as film-coated tablets. In Phase 3 clinical trials, it was tested at a dose of 60 mg, taken once daily. If approved by the FDA, tolebrutinib will likely be prescribed at the same once-daily 60 mg dose.

Tolebrutinib in MS clinical trials

Sanofi’s application seeking FDA approval of tolebrutinib was based on data from three Phase 3 clinical trials.

• The first two, dubbed GEMINI 1 (NCT04410978) and GEMINI 2 (NCT04410991), collectively enrolled 1,873 adults with relapsing forms of MS and randomly assigned them to receive tolebrutinib or the approved therapy Aubagio (teriflunomide). After up to three years of treatment with tolebrutinib or Aubagio, participants had similar rates of both relapse and new or enlarging lesions. There were also trends toward a greater number of new lesions with active inflammation in patients given tolebrutinib, showing it did not outperform Aubagio at reducing disease activity. However, fewer patients given tolebrutinib experienced six-month confirmed disability worsening (8.3% vs. 11.3) — representing a significant, 29% lower risk of progression.
• The third study, called HERCULES (NCT04411641), enrolled 1,131 adults with nonrelapsing SPMS who had evidence of disability progression despite not experiencing a relapse in the two years before entering the trial. Participants were randomly assigned to take tolebrutinib or a placebo for up to four years, and results showed that the risk of six-month confirmed disability progression was 31% lower with tolebrutinib, meeting the trial’s main goal. The experimental therapy also increased the odds of six-month confirmed disability improvement by 88%, and reduced the rate of new or enlarging lesions on MRI scans by 38%.

A fourth Phase 3 trial called PERSEUS (NCT04458051) is also comparing tolebrutinib against a placebo in 767 people with primary progressive MS. The trial aimed to demonstrate that tolebrutinib could delay the onset of six-month composite confirmed disability progression. However, that goal was not met, leading Sanofi to announce it would no longer pursue regulatory approval for this indication.

Tolebrutinib side effects

The most common adverse events of tolebrutinib reported in MS Phase 3 clinical trials included:

• COVID-19
• the common cold
• urinary tract infection
• headache
• hair loss

Some patients also experienced elevations in certain liver enzymes, a sign of liver damage, but most of these cases happened before a change in trial protocol that included more frequent liver monitoring.

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