Twice-daily MS pill cuts relapses by a third against older tablet

A twice-daily pill from Novartis has cut relapses in people with relapsing multiple sclerosis (MS) by about a third compared with teriflunomide, an established oral treatment, in two large phase 3 trials. The drug, remibrutinib, also sharply reduced new inflammation on brain scans and, unlike some medicines in its class, showed no sign of liver harm.

The REMODEL-1 and REMODEL-2 results were presented as a late-breaking abstract at MSToronto2026, the 10th joint meeting of ACTRIMS and ECTRIMS, on 23 October 2026 at 11:25 Toronto time (17:25 in Madrid). They were published the same day in The Lancet, with Professor Heinz Wiendl of the University of Freiburg as first author.

The findings matter because remibrutinib belongs to a family of drugs called BTK inhibitors, which many neurologists hoped would change MS treatment. That family has had a bumpy run. Some trials have succeeded, others have failed, and liver injury has dogged at least one rival. REMODEL is the first time a BTK inhibitor has beaten an active treatment for relapsing MS in two matching phase 3 trials.

What relapsing MS is

Multiple sclerosis is a long-term condition in which the immune system attacks myelin, the fatty coating that protects nerve fibres in the brain, optic nerves and spinal cord. Damage to myelin slows or blocks nerve signals and can cause problems with vision, movement, balance, sensation, bladder control, fatigue and thinking.

MS affects millions of people worldwide. Most people are first diagnosed with the relapsing form, in which periods of new or worsening symptoms, called relapses, are followed by partial or full recovery. Over time, many people build up disability, either from incomplete recovery after relapses or from slow, steady worsening that happens in the background.

Treatments that reduce relapses and new brain lesions are now common. They range from older injections to tablets such as teriflunomide, and to strong antibody infusions that deplete B cells, a type of white blood cell. Each comes with trade-offs between how well it works, how it is taken and what side effects it causes.

How remibrutinib works

Bruton's tyrosine kinase, or BTK, is an enzyme that helps switch on B cells and some innate immune cells, including microglia, the resident immune cells of the brain. Blocking BTK is meant to calm these cells without wiping them out.

Remibrutinib is a highly selective oral BTK inhibitor that binds permanently to its target. Novartis says it is designed to dampen BTK signalling without chronic B-cell depletion, the approach used by antibody drugs such as ocrelizumab. The medicine is already approved, under the name Rhapsido, for chronic spontaneous urticaria, a long-lasting form of hives, according to the analysis service CT Analytics.

The REMODEL trials

REMODEL-1 and REMODEL-2 were two identical, randomised, double-blind trials run at 407 centres in 46 countries. They used a double-dummy design, so everyone took both a real pill and a dummy pill and nobody knew which drug they were getting.

Adults aged 18 to 55 with relapsing MS, recent disease activity and an Expanded Disability Status Scale (EDSS) score of 0 to 5.5 were eligible. They were randomly assigned to remibrutinib 100 mg twice daily or teriflunomide 14 mg once daily. Follow-up lasted up to 30 months.

Between December 2021 and December 2025, 2,632 people were screened and 2,007 were randomised:

The main measure was the annualised relapse rate, the average number of confirmed relapses per patient per year.

Fewer relapses

Remibrutinib met the main goal in both trials.

• In REMODEL-1, the relapse rate was 0.073 per year with remibrutinib and 0.112 with teriflunomide (rate ratio 0.648, 95% confidence interval 0.453 to 0.927, p=0.018).
• In REMODEL-2, it was 0.080 against 0.116 (rate ratio 0.688, 0.487 to 0.972, p=0.034).

Novartis describes these as relative reductions of 35.2% and 31.2%. On remibrutinib, that works out at roughly one relapse every 13 years, according to the company.

Both groups had very low relapse rates. That reflects the effectiveness of teriflunomide, a modern treatment, as well as the kind of patients now recruited to MS trials. The absolute difference is small, about four relapses fewer per 100 patient-years.

Less activity on brain scans

MRI scans tell a sharper story. According to Novartis, remibrutinib beat teriflunomide on all key secondary endpoints in each trial.

New or enlarging T2 lesions, which reflect accumulated damage, fell from 2.71 to 0.94 in REMODEL-1 and from 2.77 to 0.82 in REMODEL-2. Lesions that light up with gadolinium contrast, a sign of active inflammation, fell from 0.24 to 0.08 in REMODEL-1 and from 0.21 to 0.07 in REMODEL-2. By our calculation, that is roughly 65% to 70% fewer new lesions.

Serum neurofilament light chain, a blood marker released when nerve fibres are damaged, was 9.0% lower with remibrutinib in REMODEL-1 and 7.0% lower in REMODEL-2.

In a pooled analysis, 55.0% of people on remibrutinib showed no evidence of disease activity across relapses, disability progression and MRI, against 32.1% on teriflunomide. Novartis notes this difference was nominally significant, which means it was not part of the formal chain of statistical tests.

The disability question

Disability is the outcome that people with MS care about most, and here the evidence is weaker.

In the pooled analysis, remibrutinib reduced the risk of disability progression confirmed at six months by 29.2%, but this was only nominally significant. Progression confirmed at three months fell by 20.5%, which Novartis calls a consistent positive trend; it was not statistically significant. Medscape's coverage, which included comment from Dr Shiv Saidha, made the same point: the three-month result did not reach significance and the six-month result was only nominal.

Novartis says more than 92% of people on remibrutinib stayed free of six-month confirmed progression over 24 months. Without the matching figure for teriflunomide, that number is hard to interpret on its own.

The trials were designed around relapses. Disability progression in relapsing MS is relatively uncommon over two years, so even large trials struggle to show a clear effect. Longer follow-up and the ongoing extension studies will be needed.

Safety and the liver

Liver safety was the issue people were watching. Tolebrutinib, a rival BTK inhibitor from Sanofi, has been linked to cases of serious liver injury. In REMODEL there were no cases meeting Hy's Law, a standard warning sign of drug-induced liver injury, according to Novartis.

Liver enzyme rises were in fact less common with remibrutinib. ALT, a liver enzyme, rose above three times the upper limit of normal in 2.0% of people on remibrutinib and 7.4% on teriflunomide. Teriflunomide itself is known to affect the liver.

The most common side effects, according to the Lancet abstract, were:

Adverse events led to stopping treatment in 3.1% on remibrutinib and 5.8% on teriflunomide. Serious adverse events occurred in 6.0% and 7.0%. Two people died in the remibrutinib group, one from accidental carbon monoxide poisoning and one by suicide; investigators judged neither to be related to the drug.

How it fits with other BTK inhibitors

The BTK story in MS has split by drug and by type of disease. According to CT Analytics, Roche's fenebrutinib was non-inferior to ocrelizumab in primary progressive MS in the FENtrepid trial, while Sanofi's tolebrutinib failed to delay disability in primary progressive MS in the PERSEUS trial.

REMODEL adds a clear win in relapsing MS. It does not answer whether remibrutinib is as good as the strongest antibody treatments. Novartis is testing that directly in RESHAPE, a phase 3b trial against ocrelizumab, and is also studying the drug in non-relapsing secondary progressive MS.

Expert views

"The REMODEL trial results showed that oral remibrutinib delivered a significant reduction in relapse activity while also showing a clinically meaningful effect on confirmed disability progression in people living with relapsing MS," Professor Wiendl said in the Novartis announcement.

Shreeram Aradhye, chief medical officer at Novartis, said the company believed remibrutinib had the potential to support long-term disease management without chronic B-cell depletion.

Independent commentators were more cautious about disability. The relapse and MRI results are strong, but the progression benefit rests on outcomes that were nominally significant or not significant.

Limits of the evidence

• The comparator was teriflunomide, a moderate-efficacy drug. Beating it does not show that remibrutinib matches high-efficacy infusions.
• The absolute relapse difference is small because relapse rates were low in both groups.
• Disability benefits are not proven.
• The trials ran for up to 30 months, so longer-term safety, including infections, is still being studied in extensions.
• Novartis funded and helped run the trials.

What it means for people with MS

Remibrutinib is not approved for MS anywhere yet. Novartis says it plans to seek approval worldwide. If regulators agree, it could offer a tablet option with stronger relapse and MRI control than teriflunomide, a reassuring liver profile so far, and no B-cell depletion.

Anyone with MS who is interested should talk to their neurologist. No one should stop or switch treatment because of these results alone.

This article explains published research and isn't medical advice. Talk to your own doctor or specialist team before changing any treatment.