Remibrutinib Demonstrates Superior Efficacy in Relapsing MS: A Milestone in BTK Inhibition

By Judy George, Deputy Managing Editor, MedPage Today
October 25, 2026

In a significant development for the landscape of multiple sclerosis (MS) treatment, new phase III clinical data suggests that the Bruton’s tyrosine kinase (BTK) inhibitor remibrutinib offers superior relapse control compared to the current standard of care, teriflunomide (Aubagio). The findings, presented at the joint meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) and the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) in Toronto, mark a potential turning point in how clinicians approach relapsing forms of the disease.

Crucially, the trials—REMODEL-1 and REMODEL-2—addressed one of the most pressing concerns regarding the BTK inhibitor class: hepatotoxicity. Unlike previous iterations of this drug class, which have been shadowed by concerns regarding drug-induced liver injury, remibrutinib demonstrated a clean safety profile, with no signal of liver safety risks emerging during the trials.

Main Facts: A Paradigm Shift in Relapse Reduction

The twin phase III trials, REMODEL-1 and REMODEL-2, evaluated the efficacy and safety of 100 mg of oral remibrutinib administered twice daily against the established efficacy of 14 mg of teriflunomide once daily. The primary objective was to determine if remibrutinib could outperform the existing oral standard in reducing annualized relapse rates (ARR).

The results were statistically significant across both studies. In REMODEL-1, the ARR was 0.073 for those on remibrutinib compared to 0.112 for the teriflunomide cohort (rate ratio [RR] 0.648, 95% CI 0.453-0.927, P=0.018). The REMODEL-2 trial mirrored these findings, showing an ARR of 0.080 for remibrutinib versus 0.116 for teriflunomide (RR 0.688, 0.487-0.972, P=0.034).

According to Heinz Wiendl, MD, of the University of Freiburg in Germany, the clinical translation of these numbers is profound. "The relapse rate with remibrutinib translates to approximately one relapse in 13 years," Wiendl noted during his presentation. This level of disease control represents a substantial improvement for patients who currently struggle with the frequent breakthrough activity associated with older oral therapies.

Chronology: The Journey to Phase III Success

The development of remibrutinib follows a rapid trajectory in the pharmaceutical sector. Originally investigated for its potent immune-modulating properties, the drug was previously approved under the brand name Rhapsido in a 25-mg formulation for the treatment of chronic spontaneous urticaria and symptomatic dermographism.

The decision to pivot toward multiple sclerosis was driven by the urgent need for therapies that could cross the blood-brain barrier to target both peripheral immune cells and the compartmentalized inflammation within the central nervous system.

• Pre-clinical phase: Initial studies established remibrutinib as a highly selective, covalent BTK inhibitor, suggesting it could modulate B-cell activity and microglial activation without the broader, non-selective immunosuppression seen in earlier monoclonal antibody treatments.
• REMODEL-1 & 2 Initiation: The trials were launched in late 2021, targeting patients aged 18 to 55 with relapsing MS, evidence of recent disease activity, and an Expanded Disability Status Scale (EDSS) score between 0 and 5.5.
• The 2026 Data Reveal: The simultaneous publication of the results in The Lancet and the presentation at the joint ECTRIMS/ACTRIMS meeting in Toronto represent the culmination of five years of rigorous clinical evaluation.

Supporting Data: Lesion Reduction and Axonal Protection

Beyond relapse rates, the trials looked at key secondary endpoints that serve as surrogates for long-term disease progression. The data provided a compelling case for remibrutinib’s efficacy in preventing structural damage within the brain.

Reduction in T2 and Gadolinium-Enhancing Lesions

In terms of imaging, remibrutinib showed remarkable efficacy. In REMODEL-1, there was a 65% reduction in new or enlarging T2 lesions compared to teriflunomide, while REMODEL-2 showed a 70% reduction. Even more striking was the impact on gadolinium-enhancing lesions—a hallmark of active inflammation—which were reduced by 66% in both trials.

Neurofilament Light Chain (NfL) Markers

The study also utilized serum neurofilament light chain (NfL) as a biomarker for axonal injury. Monitoring these levels provides a real-time window into neuronal damage. At 12 months, patients treated with remibrutinib exhibited significantly lower NfL levels compared to those on teriflunomide, with geometric mean ratios of 0.91 (P=0.0001) in REMODEL-1 and 0.93 (P=0.0036) in REMODEL-2.

Disability Progression

The trials also tracked 3-month and 6-month confirmed disability progression (CDP). While the 3-month reduction did not reach statistical significance (HR 0.80, P=0.090), the 6-month CDP showed a statistically significant risk reduction with remibrutinib (HR 0.70, 95% CI 0.51-0.98, P=0.038). This suggests that the therapy may be particularly effective in delaying the onset of long-term, irreversible disability.

Official Responses and Safety Profile

The safety profile of remibrutinib was a central focus of the conference, particularly given the historical scrutiny surrounding BTK inhibitors and liver enzyme elevations.

The "Liver Signal" Question

When asked about the potential for drug-induced liver injury, Dr. Wiendl was clear: "We haven’t seen really a liver signal at all." He noted that there were no cases meeting the criteria for Hy’s Law, the gold-standard prediction model for fatal drug-induced liver injury. Any transient elevations in liver enzymes observed during the trial were infrequent and resolved spontaneously without the need for treatment discontinuation.

Adverse Events and Discontinuation

The most frequently reported adverse events included:

• Upper respiratory tract infection: 13.1% (remibrutinib) vs 13.7% (teriflunomide).
• Nasopharyngitis: 9.1% vs 12.3%.
• Diarrhea: 8.3% vs 10.9%.
• Alopecia: 5.8% vs 13.5%.

Notably, discontinuation rates due to adverse events were significantly lower in the remibrutinib group (3.1%) compared to the teriflunomide group (5.8%).

One area of note was an increase in bleeding events—12.7% in the remibrutinib group versus 6.7% in the teriflunomide group. However, these were characterized as mild, transient skin manifestations, consistent with the known class effects of BTK inhibitors, which can affect platelet function.

Regarding mortality, two deaths occurred in the remibrutinib arm. One was attributed to carbon monoxide poisoning (ruled not a suicide), and the other was a suicide in a patient with a documented history of psychiatric illness. Both were deemed unrelated to the investigational drug.

Implications for the Future of MS Care

The success of the REMODEL trials positions remibrutinib as a potential leader in the next generation of oral MS therapies. By effectively balancing high-potency disease control with a favorable safety profile, it addresses the "therapeutic gap" for patients who require more than what existing oral medications offer but may be wary of the safety risks associated with some of the newer, more aggressive monoclonal antibodies.

Regulatory Outlook

Novartis, the manufacturer of remibrutinib, has confirmed its intention to pursue global regulatory approval for the drug as a treatment for relapsing forms of MS. Given the robustness of the data, the medical community expects a swift review process.

Broadening the Horizon

The implications of this drug may extend beyond MS. Because remibrutinib acts on the underlying immune-mediated mechanisms of disease, it is currently being studied for other chronic conditions, including hidradenitis suppurativa and food allergies.

For the MS patient population, the REMODEL data offers a glimmer of hope: a future where disease progression can be significantly stalled with a twice-daily pill, without the looming shadow of severe liver toxicity. As the neurology community digests these findings, the focus will now shift to long-term real-world effectiveness and the potential for combination therapies that could further improve outcomes for the millions living with MS worldwide.