Remibrutinib Cuts MS Relapses by Up to 35% in Phase 3 Trials

Novartis reported full results from the Phase 3 REMODEL-1 and REMODEL-2 trials showing that remibrutinib, an oral Bruton’s tyrosine kinase (BTK) inhibitor, reduced relapse rates in adults with relapsing multiple sclerosis (RMS) compared with teriflunomide. Presented at MSToronto2026, the 10th Joint ACTRIMS-ECTRIMS Meeting, on October 23, 2026, the findings were published simultaneously in The Lancet. Novartis plans to seek regulatory approval for remibrutinib in RMS globally.

Two Phase 3 Trials Against an Established Oral Therapy

REMODEL-1 (NCT05147220) and REMODEL-2 (NCT05156281) were multicentre, randomized, double-blind, active-controlled trials involving approximately 2,000 adults with recent disease activity and Expanded Disability Status Scale (EDSS) scores of 0.0–5.5. Participants were randomized 1:1 to receive remibrutinib 100 mg or teriflunomide.

The double-blind core period lasted up to 30 months, followed by an open-label extension of up to five years. Annualized relapse rate (ARR) was the primary endpoint in both trials.

Relapse Rates Fell by 31%–35%

Remibrutinib met the primary endpoint in both studies. In REMODEL-1, ARR was 0.073 with remibrutinib versus 0.112 with teriflunomide, representing a 35.2% relative reduction. In REMODEL-2, the corresponding rates were 0.080 versus 0.116, a 31.2% reduction.

Novartis described these results as equivalent to approximately one relapse every 13 years. This is a rate-based illustration of the trial findings, not a prediction of how frequently an individual patient will experience a relapse.

The consistency across two independent Phase 3 trials strengthens the evidence for relapse reduction against the active comparator. However, the studies do not establish superiority over other high-efficacy disease-modifying therapies for MS.

MRI Findings Support Reduced Disease Activity

Remibrutinib also reduced MRI measures of disease activity. Annualized T2 lesion activity was 0.94 versus 2.71 in REMODEL-1 and 0.82 versus 2.77 in REMODEL-2, representing reductions of 65% and 70%, respectively.

Gadolinium-enhancing T1 lesions per scan were 0.08 versus 0.24 in REMODEL-1 and 0.07 versus 0.21 in REMODEL-2, a reduction of approximately 66% in both trials.

Serum neurofilament light chain, a biomarker associated with neuroaxonal injury, was 9.0% lower with remibrutinib in REMODEL-1 and 7.0% lower in REMODEL-2.

In the prespecified pooled analysis, 55.0% of remibrutinib-treated participants achieved no evidence of disease activity across relapses, disability progression and MRI findings (NEDA-3), compared with 32.1% receiving teriflunomide. The difference was nominally significant and should not be interpreted as definitive proof of broader disease control.

Disability Progression Remains an Unconfirmed Benefit

The pooled analysis showed a 29.2% reduction in the risk of six-month confirmed disability progression (6mCDP), with nominal statistical significance. Three-month confirmed disability progression was reduced by 20.5%, representing a positive trend.

More than 92% of participants receiving remibrutinib remained free from six-month confirmed disability progression over 24 months.

These findings are encouraging, but their statistical status matters. Nominal significance does not establish a confirmatory treatment effect when the result falls outside the formal testing hierarchy. The results therefore support further evaluation of disability outcomes rather than establishing that remibrutinib prevents long-term disability progression.

Liver Safety Findings Are Reassuring Within the Trials

Novartis reported no liver safety signal and no cases meeting Hy’s Law criteria. Alanine aminotransferase (ALT) elevations exceeding three times the upper limit of normal occurred in 2.0% of remibrutinib-treated participants versus 7.4% receiving teriflunomide.

Overall adverse events occurred in 79.5% versus 81.5% of participants, serious adverse events in 6.0% versus 7.0%, and adverse-event-related discontinuations in 3.1% versus 5.8%, respectively.

Two deaths occurred in the remibrutinib group. Investigators judged both unrelated to treatment: one followed accidental carbon monoxide poisoning, with suicide ruled out, and the other was a completed suicide.

The reported findings are reassuring, but they do not establish an absence of liver risk during longer-term use. Continued follow-up will help characterize the treatment’s safety profile.

Regulatory Outlook and Clinical Implications

Remibrutinib is already marketed as Rhapsido for chronic spontaneous urticaria, following US approval in September 2025, UK authorization in August 2026 and European authorization in April 2026. The US FDA approved it for symptomatic dermographism in October 2026. Novartis is also investigating remibrutinib in secondary progressive MS through the REMASTER programme.

The REMODEL results establish replicated reductions in relapses and MRI activity versus teriflunomide. They also provide a nominal signal for disability progression, which requires cautious interpretation. The trials do not establish superiority over high-efficacy MS therapies, and the proposed advantage of avoiding chronic B-cell depletion remains a mechanistic distinction rather than a demonstrated comparative clinical benefit.

The findings support Novartis’ planned regulatory submissions, while the ultimate clinical position of remibrutinib will depend on the full evidence, longer-term safety and its comparative value against available MS treatments.

Reference

Novartis remibrutinib delivered comprehensive disease control in Phase III RMS trials, with proven, robust safety profile, Novartis, 23 October 2026

Wiendl H, Bermel R, Airas L et al., Remibrutinib versus teriflunomide in relapsing multiple sclerosis (REMODEL-1 and REMODEL-2): two randomised, phase 3 trials, The Lancet, October 23, 2026, https://doi.org/10.1016/S0140-6736(26)02058-1

Efficacy and Safety of Remibrutinib Compared to Teriflunomide in Participants With Relapsing Multiple Sclerosis (RMS) (REMODEL-1), ClinicalTrials.gov ID NCT05147220

Efficacy and Safety of Remibrutinib Compared to Teriflunomide in Participants With Relapsing Multiple Sclerosis (RMS) (REMODEL-2), ClinicalTrials.gov ID NCT05156281