European drug regulators recommended approval of tolebrutinib, branded as Cenrifki, on April 24 for adults with non-relapsing secondary progressive MS, a form of the disease where disability steadily worsens without the episodic relapses that characterize earlier MS stages. The European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) issued a positive opinion, which typically leads to European Commission approval within months. If the drug later gains FDA approval, it would mark the first treatment shown to meaningfully slow disability progression in this MS population.

What Non-Relapsing Secondary Progressive MS Is

Secondary progressive MS (SPMS) is a stage of MS that typically follows years of relapsing-remitting disease. In the relapsing form, people experience distinct flare-ups (relapses) followed by periods of recovery. In secondary progressive MS, that pattern shifts. Disability accumulates steadily, with or without relapses.

Non-relapsing SPMS is the subset where there's been no relapse activity for at least two years. You're watching function decline without the dramatic flare that might trigger a treatment adjustment. The immune system continues attacking the nervous system through what researchers call smoldering neuroinflammation, a slower-burning process that current relapse-focused therapies don't address.

An estimated 400,000 Americans live with MS. A significant portion will eventually transition to secondary progressive disease, and many of those will enter the non-relapsing phase. Until now, there hasn't been an FDA-approved drug specifically proven to slow that progression.

What the HERCULES Trial Showed

The CHMP recommendation is based on data from the HERCULES Phase 3 trial, which enrolled adults with non-relapsing SPMS. Participants who took tolebrutinib showed a 31% reduction in six-month confirmed disability progression compared to those on placebo.

That outcome is measured using the Expanded Disability Status Scale (EDSS), a standard MS disability metric that tracks mobility, vision, cognition, and other functional domains. Six-month confirmation means the worsening persisted at a follow-up assessment, reducing the chance that a temporary setback was mistaken for true progression.

Tolebrutinib is a Bruton's tyrosine kinase (BTK) inhibitor, an oral medication designed to cross the blood-brain barrier and target the inflammatory activity driving disability accumulation in progressive MS. It's not a cure and it doesn't reverse existing damage. It slows the rate at which new disability accumulates.

Safety Profile and Liver Monitoring

Drug-induced liver injury (DILI) is an identified risk. The most common adverse events in the trial were COVID-19 and upper respiratory tract infections, but significant liver enzyme elevations were also observed in some participants.

If the drug receives final approval, liver function monitoring will be required. Families considering this treatment will need to factor in regular blood work and the possibility of stopping the drug if liver markers rise above safe thresholds.

The FDA rejected Sanofi's application for tolebrutinib in late 2025, citing liver safety concerns. The CHMP's positive opinion in Europe doesn't guarantee FDA approval in the US. It does, however, signal that European regulators found the benefit-risk profile acceptable with appropriate monitoring protocols in place.

What This Means for Families

This regulatory milestone doesn't immediately change treatment options in the US. The European Commission's final decision is expected in the coming months. If approved in Europe, Sanofi may resubmit to the FDA with additional safety data or revised monitoring requirements.

For families living with non-relapsing SPMS, this represents the first regulatory validation of a drug that targets the specific biology driving disability in their situation. Current disease-modifying therapies (DMTs) for MS are designed to prevent relapses. They've shown limited or no benefit in slowing progression once the disease shifts to the non-relapsing secondary progressive stage.

If tolebrutinib eventually reaches the US market, it would provide a pharmacological option where none currently exists for this population. The 31% reduction in disability progression observed in the trial translates to real-world impact in how long someone maintains the ability to walk unassisted, manage self-care, or continue working.

What Families Can Do Now

If your neurologist has diagnosed non-relapsing SPMS, meaning you've had no relapses in the past two years, you can:

• Ask whether you'd be a candidate for tolebrutinib if it becomes available in the US, based on your disease history and liver function
• Discuss the current FDA status and whether your care team expects a resubmission
• Review your current treatment plan to confirm it's appropriate for progressive disease rather than relapsing disease
• Request baseline liver function testing now, so you have a reference point if the drug becomes an option later

The CHMP positive opinion is public. The full European Commission decision typically follows within three months. If approved in the EU, US advocacy organizations and MS specialty clinics will likely push for FDA reconsideration.

You can find the CHMP meeting highlights on the European Medicines Agency website, and Sanofi has published the full press release detailing the HERCULES trial outcomes and safety profile.