Novartis remibrutinib meets Phase III endpoints in relapsing MS

Novartis has presented pivotal Phase III data for remibrutinib in relapsing multiple sclerosis (RMS), reporting that the oral BTK inhibitor outperformed the established comparator teriflunomide on both relapse control and disability progression in two identically designed trials.

Results from REMODEL-1 and REMODEL-2 were unveiled during a late-breaking session at MSToronto2026, the 10th Joint ACTRIMS-ECTRIMS Meeting, and published simultaneously in The Lancet on 23 October 2026.

Trial results

The primary endpoint in both studies was annualised relapse rate (ARR). Remibrutinib achieved ARRs of 0.073 and 0.080 in REMODEL-1 and REMODEL-2 respectively, versus 0.112 and 0.116 for teriflunomide. The relative reductions of 35.2% and 31.2% translate, by Novartis's calculation, to approximately one relapse every 13 years. More than 92% of patients on remibrutinib remained free from six-month confirmed disability progression (6mCDP) over 24 months, with a nominally significant 29.2% reduction in that risk versus teriflunomide.

MRI outcomes reinforced the clinical picture. Annualised T2 lesion activity fell by roughly 65% and 70% in REMODEL-1 and REMODEL-2, and gadolinium-enhancing T1 lesion rates were reduced by 66% across both trials when compared with teriflunomide. Serum neurofilament light chain, a biomarker of neuronal injury, improved by 9.0% and 7.0% in the two studies. In the pooled analysis, 55% of remibrutinib patients achieved NEDA-3 (no evidence of disease activity across relapses, disability, and MRI) versus 32.1% on teriflunomide.

The safety profile drew particular attention in a class where liver toxicity has proved problematic. Novartis reported no Hy's Law cases with remibrutinib, and ALT elevations above three times the upper limit of normal occurred in 2.0% of remibrutinib patients compared with 7.4% on teriflunomide. Treatment discontinuations due to adverse events were 3.1% versus 5.8% in the pooled dataset.

"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 Prof. Dr. Heinz Wiendl, Chair of Neurology at the Medical Center, University of Freiburg. "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 RMS."

Competitive landscape and regulatory path

The BTK inhibitor class has had a turbulent passage in MS. Tolebrutinib, developed by Sanofi, generated liver safety concerns that delayed regulatory progress, and evobrutinib, Merck KGaA's candidate, produced mixed Phase III readouts. Remibrutinib's clean liver signal in a 2,000-patient dataset distinguishes it meaningfully at this stage, though regulators will scrutinise long-term extension data before drawing firm conclusions.

Remibrutinib already carries regulatory approval under the brand name Rhapsido for chronic spontaneous urticaria, granted by the FDA in September 2025 and by the European Medicines Agency in April 2026. A further FDA approval for symptomatic dermographism followed in October 2026. That existing safety database provides additional context for the REMODEL findings, though the RMS dose of 100 mg is higher than the 25 mg urticaria approval.

Novartis said it plans to seek regulatory approval for remibrutinib in RMS globally, though it gave no specific filing timeline. A separate Phase III trial, REMASTER, is underway in secondary progressive MS, broadening the potential indication set. The MS market remains one of the most commercially significant in neurology, with approved high-efficacy therapies including natalizumab, ocrelizumab, and ofatumumab setting a high bar for any new entrant. Remibrutinib's oral route, combined with the avoidance of chronic B-cell depletion, represents a positioning argument Novartis will need to substantiate through longer-term outcome data and head-to-head comparisons.