Remibrutinib Meets Primary End Point in Phase 3 REMODEL Trials for Relapsing Multiple Sclerosis

Novartis has announced that its oral investigational Bruton tyrosine kinase (BTK) inhibitor remibrutinib met the primary end point in the phase 3 REMODEL-1 (NCT05147220) and REMODEL-2 trials (NCT05156281), significantly reducing annualized relapse rate (ARR) compared with teriflunomide (Aubagio; Sanofi) in patients with relapsing multiple sclerosis (RMS).¹ Remibrutinib also demonstrated superiority over teriflunomide on all prespecified key secondary end points in each trial, including reduction of new inflammatory brain lesions on MRI.

"Despite advances in treatment, an unmet need remains for oral therapies that can deliver robust relapse prevention, slow disability progression, while maintaining a favorable safety profile," Shreeram Aradhye, MD, president of development and chief medical officer at Novartis, said in a statement.¹ "The positive REMODEL results underscore the potential of remibrutinib as a high-efficacy oral therapy for people living with RMS with a differentiated benefit-risk profile. Building on our long-standing commitment to advancing care in MS, these findings reinforce our continued ambition on driving innovation in this space and delivering therapies that address the evolving needs of people living with MS.”

REMODEL-1 and REMODEL-2 are identical multicenter, randomized, double-blind, active comparator-controlled trials that enrolled approximately 2000 adults globally with RMS and evidence of recent disease activity, with Expanded Disability Status Scale scores of 0.0 to 5.5.¹ Participants were randomized 1:1 to remibrutinib 100 mg or teriflunomide, an FDA-approved oral disease-modifying therapy that served as the active comparator. Each trial included a double-blind core period of up to 30 months followed by an open-label extension of up to 5 years. Key secondary end points included 3- and 6-month confirmed disability progression (3mCDP, 6mCDP), annualized new or enlarging T2 lesions, gadolinium-enhancing T1 lesions per scan, serum neurofilament light chain concentration, and the proportion of patients with no evidence of disease activity.

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In a preplanned combined analysis of the 2 trials, remibrutinib showed a positive trend in 3mCDP and reached nominal significance for 6mCDP versus teriflunomide. Novartis noted that full results are expected at a late-breaking presentation at MSToronto2026, the joint ECTRIMS-ACTRIMS meeting, held October 21-23, in Toronto, Canada, to be followed by an investor call. The company reported a favorable safety profile with no liver safety signal and no cases meeting Hy’s law criteria, consistent with the broader remibrutinib program, which spans more than 4500 participants across neurologic and immune-mediated indications.

MS is a chronic inflammatory disease of the central nervous system marked by demyelination and axonal injury, and its global prevalence and diagnosed incidence have risen over the past 2 decades.² RMS, encompassing clinically isolated syndrome, relapsing-remitting MS, and active secondary progressive MS, is the most common disease course and is defined largely by relapses. Available oral disease-modifying therapies, including teriflunomide, sphingosine-1-phosphate modulators, and fumarates, vary in efficacy and require ongoing safety monitoring. An oral agent approaching the relapse and lesion control of higher-efficacy infused therapies, without added immunosuppressive burden, would address a recognized gap in RMS management.

Remibrutinib is a highly selective, covalent oral BTK inhibitor that blocks B-cell receptor and Fc receptor signaling, limiting activation of B cells and innate immune cells implicated in MS-related neuroinflammation. Novartis is also evaluating the drug in REMASTER (NCT07225504), a phase 3 trial in nonrelapsing secondary progressive MS, and in hidradenitis suppurativa and peanut allergy.¹ The molecule previously reached the US market as Rhapsido, approved by the FDA in September 2025 and by the European Medicines Agency in April 2026 for chronic spontaneous urticaria, based on phase 3 data showing reduced urticaria activity scores versus placebo with a tolerability profile similar to placebo.³

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REFERENCES
1. Novartis remibrutinib, a high-efficacy oral BTK inhibitor, significantly reduces relapse rates and shows favorable safety profile in Phase III RMS trials. News release. Novartis. September 1, 2026. Accessed September 1, 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
2. Portaccio E, Magyari M, Havrdova EK, et al. Multiple sclerosis: emerging epidemiological trends and redefining the clinical course. Lancet Reg Health Eur. 2024;44:100977. Published 2024 Aug 22. doi:10.1016/j.lanepe.2024.100977
3. Novartis receives FDA approval for Rhapsido® (remibrutinib), the only oral, targeted BTKi treatment for chronic spontaneous urticaria (CSU). GlobeNewswire News Room. September 30, 2025. Accessed September 1, 2026. https://www.novartis.com/us-en/news/media-releases/novartis-receives-fda-approval-rhapsido-remibrutinib-only-oral-targeted-btki-treatment-chronic-spontaneous-urticaria-csu