Remibrutinib Cuts Multiple Sclerosis Relapse Rates In Phase III Trials

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Two Phase III trials found that twice-daily remibrutinib lowered annualized relapse rates compared with teriflunomide in people with relapsing multiple sclerosis. Some disability and imaging measures also favored remibrutinib, but the three-month disability result was not statistically significant; Novartis says it plans to seek regulatory approval globally.

Twice-daily remibrutinib lowered annualized relapse rates compared with teriflunomide in two Phase III trials involving people with relapsing multiple sclerosis, according to results presented at MSToronto2026 and published in The Lancet. The findings support Novartis’ plan to seek regulatory approval for the drug in relapsing MS, though the studies did not show a statistically significant benefit on one measure of confirmed disability progression.

In REMODEL-1, the annualized relapse rate was 0.073 with remibrutinib and 0.112 with teriflunomide, also known as Aubagio. The rate ratio was 0.648 (95% confidence interval 0.453 to 0.927; P=0.018). In REMODEL-2, the rates were 0.080 and 0.116, respectively, with a rate ratio of 0.688 (95% confidence interval 0.487 to 0.972; P=0.034). Both comparisons favored remibrutinib.

The trials tested 100 mg of remibrutinib twice daily against 14 mg of teriflunomide once daily. REMODEL-1 enrolled 1,000 people and REMODEL-2 enrolled 1,007; participants were 18 to 55 years old, had evidence of recent disease activity, and had baseline Expanded Disability Status Scale scores from 0 to 5.5. Average baseline scores were about 2.5.

Other outcomes were mixed. The percentage with three-month confirmed disability progression in pooled trial data was 11.7% with remibrutinib and 14.1% with teriflunomide, a difference that was not statistically significant (hazard ratio 0.80; P=0.090). Six-month confirmed progression occurred in 7.7% and 10.5%, respectively (hazard ratio 0.70; P=0.038). New and enlarging T2 lesions were reduced by 65% and 70% in the two trials, according to presenting investigator Heinz Wiendl; gadolinium-enhancing lesions were reduced by 66% in each.

Relapse Results and Disability Measures

The findings add evidence for an oral BTK inhibitor as a possible treatment option for relapsing MS. Lower relapse rates in both trials, alongside reductions in MRI lesion measures, suggest remibrutinib affected indicators of disease activity over the study period. The two trials used the same design and active comparator, offering results across two large study groups rather than a single trial.

The disability findings warrant a more careful reading. The pooled three-month progression comparison did not reach statistical significance, while the six-month result did. These endpoints are not interchangeable, and the reported results do not establish that remibrutinib prevents long-term disability. Follow-up and regulatory review will help clarify how the relapse and disability outcomes factor into treatment decisions.

Safety also matters for a drug in this class. The report said newly occurring liver enzyme elevations were infrequent, transient, and reversible, and no cases met Hy’s Law criteria. That is relevant because liver injury concerns have arisen in trials of other BTK inhibitors for MS. However, the trials also recorded more bleeding events with remibrutinib, a difference clinicians and regulators will need to weigh.

How the REMODEL Trials Were Run

REMODEL-1 and REMODEL-2 were randomized, identical Phase III trials comparing remibrutinib with an established MS treatment, teriflunomide. About half of each trial’s participants received remibrutinib. The average participant was 38 to 39 years old; 67% were women. Participants had experienced MS symptoms for more than six years on average and had been diagnosed for more than four years.

Remibrutinib is a Bruton’s tyrosine kinase inhibitor. A 25 mg formulation, marketed as Rhapsido, is approved for chronic spontaneous urticaria and symptomatic dermographism; that approval is separate from use in MS. Novartis is studying the drug in other immune-mediated conditions as well. The MS results were presented at the joint ECTRIMS-ACTRIMS meeting in Toronto and published in The Lancet on October 25, 2026.

“In REMODEL-1 and REMODEL-2, there is a highly significant reduction, 65% and 70%.”

— Heinz Wiendl, MD, University of Freiburg, presenting the results at MSToronto2026

Questions on Long-Term Benefit and Safety

The reported results do not establish whether remibrutinib changes long-term disability or how durable its relapse benefit will be beyond the trial follow-up reported. The three-month confirmed disability progression result was not statistically significant; the six-month result favored remibrutinib, but further evidence will be needed to understand the clinical importance of that difference.

Some safety details also need continued monitoring. Bleeding events occurred in 12.7% of remibrutinib recipients and 6.7% of teriflunomide recipients. The report characterized these events as generally mild and transient, but full assessment depends on the trial data and ongoing safety review. Two deaths occurred among remibrutinib recipients; Wiendl said one involved carbon monoxide poisoning, with suicide ruled out, and the other was a suicide in a patient with a prior psychiatric history. Both were considered unrelated to the drug.

The available report does not provide the full duration of follow-up or the complete breakdown of individual adverse events. Whether regulators will accept the evidence, and what additional data they may require, remains unknown.

Novartis Plans Global MS Filings

Novartis said it plans to seek regulatory approval globally for remibrutinib in relapsing MS. The company has not specified in the supplied report the timing of filings, the countries involved, or when a decision might be expected. Regulatory agencies will review the trial results, safety data, and proposed use before deciding whether to authorize the drug for MS.

Further details on study follow-up, the full safety profile, and how the disability outcomes develop over time will be relevant as the evidence is reviewed. Until any MS-specific authorization is granted, the existing approval of the 25 mg formulation for certain skin conditions does not mean remibrutinib is approved for multiple sclerosis.

Key Questions

What did the two Phase III trials find?

Both trials found lower annualized relapse rates with remibrutinib than with teriflunomide in people with relapsing MS. REMODEL-1 reported rates of 0.073 versus 0.112, and REMODEL-2 reported 0.080 versus 0.116.

Did remibrutinib reduce disability progression?

The pooled three-month confirmed disability progression result favored remibrutinib but was not statistically significant. The six-month result favored remibrutinib and was statistically significant. The results do not by themselves establish a long-term effect on disability.

What safety findings were reported?

The report described liver enzyme elevations as infrequent, transient, and reversible, with no cases meeting Hy’s Law criteria. Bleeding events were more common with remibrutinib than teriflunomide: 12.7% versus 6.7%.

Is remibrutinib approved to treat MS?

The source report says Novartis plans to seek global regulatory approval for remibrutinib in relapsing MS. It does not report an MS approval. A 25 mg formulation is approved for certain skin conditions, which is a separate use.

Source: rss