Experimental MS therapy outperforms approved treatment in two trials

The experimental oral therapy remibrutinib significantly reduced relapse rates and brain lesion activity more than the approved therapy Aubagio (teriflunomide) in two Phase 3 clinical trials of people with relapsing forms of multiple sclerosis (MS).

The trials, REMODEL-1 (NCT05147220) and REMODEL-2 (NCT05156281), compared remibrutinib with Aubagio in about 2,000 adults with MS, ages 18 to 55, in 46 countries.

The findings, presented last month at the 10th joint meeting of the Americas and European Committees for Treatment and Research in Multiple Sclerosis, also suggested that remibrutinib may help reduce the risk of disability progression. The therapy showed a favorable safety profile, with nearly 50% fewer participants stopping treatment because of adverse events compared with those taking Aubagio.

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Oct. 23, 2026 News by Michela Luciano, PhD

Experimental therapy may curb chronic brain inflammation in MS

How the experimental MS therapy works

Developed by Novartis, remibrutinib is designed to reduce inflammation in MS without continuously depleting B cells. These immune cells contribute to MS-related inflammation but also help the body fight infections. Based on the positive results, Novartis plans to seek approval for remibrutinib as a treatment for relapsing MS worldwide.

“The Phase III REMODEL results reinforce our confidence in remibrutinib and its potential to expand treatment choice for people living with [relapsing MS],” Shreeram Aradhye, president of development and chief medical officer at Novartis, said in a company press release. “By combining high efficacy with a favorable safety profile through a selective mechanism, remibrutinib has the potential to support long-term disease management without chronic B-cell depletion and to redefine what may be possible across the MS journey.”

The findings are also detailed in the study, “Remibrutinib versus teriflunomide in relapsing multiple sclerosis (REMODEL-1 and REMODEL-2): two randomised, phase 3 trials,” published in The Lancet.

In MS, the immune system mistakenly attacks healthy tissue in the brain and spinal cord. This causes inflammation and nerve damage, leading to a range of MS symptoms. Over time, nerve damage can contribute to worsening disability.

Remibrutinib is taken by mouth as a tablet. It is a Bruton’s tyrosine kinase (BTK) inhibitor that selectively blocks an enzyme involved in the inflammatory activity of certain immune cells, including B cells and microglia, that contribute to MS-related inflammation.

By acting on different types of immune cells, BTK inhibitors are thought to reduce inflammation that drives relapses, or periods of new or worsening symptoms. They may also reduce ongoing inflammation that contributes to worsening disability even without relapses.

Unlike certain other MS treatments, BTK inhibitors do not work by depleting B cells, which may offer advantages for long-term treatment.

Remibrutinib reduces relapses and brain lesions in trials

In the two similarly designed REMODEL trials, participants were randomly assigned to receive remibrutinib at 100 mg twice daily or Aubagio at 14 mg once daily. The main goal was to determine whether remibrutinib could reduce relapse rates more than Aubagio during up to 30 months (2.5 years) of follow-up.

As previously reported, both trials met that goal.

In REMODEL-1, the estimated annual relapse rate was 0.073 with remibrutinib, compared with 0.112 with Aubagio — a 35.2% reduction. Results were similar in REMODEL-2, where the rates were 0.080 versus 0.116, representing a 31.2% reduction.

In the MRI analysis, remibrutinib also reduced the annual rate of new or enlarging MS lesions seen on MRI scans by 65.3% in REMODEL-1 and 70.3% in REMODEL-2 compared with Aubagio. The number of lesions showing active inflammation per scan was also reduced by about 66% in both trials.

People who received remibrutinib also had a 29.2% lower risk of 6-month confirmed disability progression compared with those receiving Aubagio. This means an increase in disability that is still present at least six months later. More than 92% of those taking remibrutinib remained free from this type of disability progression over two years.

However, the reduction was only nominally statistically significant. This means it met the usual threshold for statistical significance but not the stricter requirements used when testing multiple outcomes in a clinical trial. The finding therefore suggests a potential benefit but does not conclusively establish that remibrutinib slows disability progression.

Safety findings show fewer treatment discontinuations

Remibrutinib was generally well tolerated. Adverse events were reported in 79.5% of people taking remibrutinib and 81.5% of those receiving Aubagio. Serious adverse events occurred in 6% and 7%, respectively. Fewer participants stopped treatment because of adverse events with remibrutinib (3.1% vs. 5.8%).

Marked increases in liver enzymes, which can signal liver injury, have been reported with several BTK inhibitors. In these trials, such increases occurred in 2% of people receiving remibrutinib, compared with 7.4% of those taking Aubagio. No cases meeting established criteria for potentially serious drug-related liver injury were reported.

“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,” said Heinz Wiendl, MD, professor of neurology at the University of Freiburg.

“As treatment goals in MS continue to evolve beyond relapse control alone, these efficacy findings, together with the favorable safety profile, suggest remibrutinib has the potential to deliver a meaningful, differentiated treatment option for people living with [relapsing MS],” Wiendl added.