Part 4 · Treatment
Toward a cure
No treatment cures MS today. A cure would have to stop relapses, quiet smouldering inflammation, repair myelin and protect axons. Press Play to add the four jobs to one lesion, then see where the trials stand, with every finding labelled by its strength of evidence.
What a cure would have to do
Schematic, not to scale. The four layers show what each approach aims at, not how well it works; the labels beside or below the drawing give the evidence.
The routes, and how strong the evidence is
Each finding below carries a label. Established marks a firm finding: a peer-reviewed trial result, a large cohort, a guideline, or a settled fact such as a trial missing its endpoint or a regulator's decision. Early evidence marks small, early-phase, uncontrolled or not yet peer-reviewed efficacy results. Hypothesis marks laboratory, animal or single-case work. Rejected marks an idea that later trials did not support. Findings that rest on a company press release say so. Failed trials are shown as plainly as successful ones.
One drug, two regulators
Regulators in the United States and the European Union reached different decisions on tolebrutinib for non-relapsing secondary progressive MS. Both statements below are given as the sources word them.
Complete response letter
The FDA issued a complete response letter for tolebrutinib in non-relapsing SPMS (Sanofi release, 24 December 2025), calling it a change from earlier agency feedback. The drug is not approved in the US. 419
Source: company press release. The FDA letter itself was not accessed.
Positive opinion, then authorisation
The EMA's CHMP gave a positive opinion on 23 April 2026 for tolebrutinib (Cenrifki) "for the treatment of adult patients with SPMS without relapses in the last 2 years". It cites a 31% reduction in 6-month confirmed disability progression and 38% fewer new or enlarging T2 lesions, and calls drug-induced liver injury the "most worrisome side effect". The EMA page lists the medicine as authorised on 19 June 2026, under additional monitoring, with mandatory liver testing. 124
Source: EMA summary of opinion and EPAR page.
Why they may differ. HERCULES met its primary endpoint (HR 0.69) 156, but tolebrutinib showed no meaningful benefit in primary progressive MS (PERSEUS) 303,420, and liver injury (six Hy's Law cases, one death after a liver transplant) shapes the benefit-risk debate 303. As of October 2026 the US and EU positions differ. This page reports those decisions; it is not advice about any person's treatment.
The trial results, line by line
A forest plot puts each trial on one line: the square is the main estimate and the bar its 95% confidence interval. When the bar crosses the no-effect line, the trial did not show a difference. Press Play to bring the trials in one at a time; the table below gives the same results with their sources.
Estimates as published in the trial abstracts or the sponsor's release. Rows marked "press release" have no peer-reviewed paper yet.
| Trial · registry | Comparison | Population | Main result | Verdict | Source type |
|---|
Where the experts disagree
Where this leaves us. Drugs that keep immune cells out of the brain are established. The other three jobs are not done: the International Progressive MS Alliance describes neurodegeneration and compartmentalised inflammation as "virtually untargeted" and funds experimental-medicine trials to speed things up 108, and the National MS Society's refined Pathways to Cures roadmap calls for global data sharing and sustained, coordinated funding 25. Biomarkers such as serum neurofilament light, GFAP and paramagnetic rim lesions may make trials shorter, but none is yet validated as a trial endpoint 18,232.