Novel BTK Inhibitor for Relapsing MS Investigated in Phase 3 Studies

Remibrutinib (Novartis, Basel, Switzerland), an investigational oral Bruton’s tyrosine kinase (BTK) inhibitor for the treatment of individuals with relapsing multiple sclerosis (RMS), showed significant reductions in annualized relapse rate (ARR) compared with Aubagio (teriflunomide; Paris, France) in the phase 3 REMODEL-1 (NCT05147220) and REMODEL-2 (NCT05156281) clinical trials, according to topline results announced by Novartis.

REMODEL-1 and REMODEL-2 are identical multicenter, randomized, double-blind, active comparator-controlled phase 3 trials evaluating remibrutinib treatment in adults with RMS. Approximately 2000 participants with recent disease activity and Expanded Disability Status Scale (EDSS) scores of 0.0 to 5.5 were randomly assigned 1:1 to receive remibrutinib 100 mg or Aubagio. The studies include a double-blind core period of up to 30 months, followed by an open-label extension of up to 5 years.

Topline Trial Findings

• Both REMODEL trials met the primary endpoint of ARR reduction for remibrutinib treatment vs Aubagio.
• Novartis reported that remibrutinib was superior to Aubagio on key secondary endpoints in each trial, including reductions in MRI lesions.
• In a preplanned combined analysis of REMODEL-1 and REMODEL-2, remibrutinib treatment showed a positive trend on 3-month confirmed disability progression and nominal significance on 6-month confirmed disability progression.
• Key secondary endpoints in the trials included 3- and 6-month confirmed disability progression, new or enlarging T2 lesions per year, gadolinium-enhancing T1 lesions per scan, serum neurofilament light chain concentration, and no evidence of disease activity-3.
• Novartis reported that remibrutinib was well tolerated and that no liver safety signal was observed, including no cases meeting Hy’s Law criteria.

Potential Implications for Neurologic Practice

The REMODEL results may help define how oral BTK inhibition could fit within the RMS treatment landscape alongside existing high-efficacy infusion, injectable, and oral disease-modifying therapies. For neurologists, the clinical relevance will depend on the full REMODEL data, including the magnitude of relapse reduction, MRI effects, disability outcomes, serum neurofilament light chain results, and detailed safety findings.

Novartis stated that full REMODEL-1 and REMODEL-2 data will be presented as late-breaking results at MSToronto2026 and that the company plans to seek regulatory approval for remibrutinib in RMS globally.

Source

Novartis. Novartis remibrutinib, a high-efficacy oral BTK inhibitor, significantly reduces relapse rates and shows favorable safety profile in phase III RMS trials. Published September 1, 2026. Accessed September 2, 2026. https://www.novartis.com/news/media-releases/novartis-remibrutinib-high-efficacy-oral-btk-inhibitor-significantly-reduces-relapse-rates-and-shows-favorable-safety-profile-phase-iii-rms-trials