Against a Standard MS Pill, an Experimental Tablet Cut Relapses Further

CATEGORY: BRAIN & MENTAL HEALTH

Could a new class of multiple sclerosis pill actually beat an approved therapy, not just match it? That question had a discouraging history. Two large trials now answer it: remibrutinib, an experimental tablet, had relapse rates 35.2% lower in one trial and 31.2% lower in the other than teriflunomide, a standard oral MS drug.Teriflunomide was the comparison drug in both trials.¹ Relapses were uncommon either way: roughly 7 per 100 people per year on remibrutinib versus 11 per 100 on teriflunomide.

Two Identical Trials, One Answer Twice

REMODEL-1 and REMODEL-2 enrolled 2,007 adults aged 18 to 55 with relapsing MS around the world. Each person swallowed a pill every day for up to 30 months without knowing which drug it was. Their doctors didn’t know either. A computer made the assignment before anyone could weigh in. Running the same experiment twice is a deliberate form of insurance, and here both copies landed on the same side: fewer relapses with remibrutinib, with relapse rates of 0.073 versus 0.112 in the first trial and 0.080 versus 0.116 in the second. The results were presented at the ECTRIMS-ACTRIMS meeting in Toronto and published in The Lancet.¹

Quieter Scans and Less Disability Creep

MS shows itself on MRI before a person feels anything, and the scans told the same story. New or growing brain lesions appeared at roughly a third of teriflunomide’s rate, 0.94 versus 2.71 per year in one trial and 0.82 versus 2.77 in the other. The risk of disability worsening that lasted six months was 29.2% lower in a pooled analysis, a result the investigators call nominally significant rather than definitive. Just over half of remibrutinib patients, 55%, showed no evidence of disease activity at all, against 32% on teriflunomide.¹

The Drug Class That Had Stumbled

Remibrutinib blocks Bruton’s tyrosine kinase, an enzyme that helps drive the immune cells attacking the nervous system in MS. Expectations for this class had been bruised. Evobrutinib, an earlier drug of the same type, failed to beat teriflunomide at all in its own pair of phase 3 trials, with relapse rates that were essentially identical.² That failure made these results anything but guaranteed. Safety held up too. Liver enzyme spikes, the worry that has shadowed these drugs, were less common on remibrutinib than on teriflunomide, 2.0% versus 7.4%, and slightly fewer people quit over side effects. Novartis funded both trials and says it will seek regulatory approval; remibrutinib isn’t approved for MS today. What a 30-month trial can’t say is how well the pill holds up over the decades an MS diagnosis spans.

Key Takeaways

• Remibrutinib’s relapse rate was about a third lower than teriflunomide’s, an approved oral MS therapy, in both of two identical trials.
• Brain lesion activity on MRI was roughly a third as frequent as it was with teriflunomide.
• An earlier drug in the same class couldn’t beat teriflunomide, which makes a win against an active drug notable.
• The drug remains experimental, and the trials ran 30 months in a disease that runs for decades.

References

1. Wiendl H, et al. Remibrutinib versus teriflunomide in relapsing multiple sclerosis (REMODEL-1 and REMODEL-2): two randomised, phase 3 trials. The Lancet. 2026; S0140-6736(26)02058-1. link
2. evolutionRMS investigators. Safety and efficacy of evobrutinib in relapsing multiple sclerosis (evolutionRMS1 and evolutionRMS2): two multicentre, randomised, double-blind, active-controlled, phase 3 trials. The Lancet Neurology. 2024;23(11):1119–1132. link