Remibrutinib Lowers Relapse Rate vs Teriflunomide in Relapsing MS

Remibrutinib (Novartis), an oral Bruton tyrosine kinase (BTK) inhibitor, reduced annualized relapse rate (ARR) vs teriflunomide in 2 phase 3 trials of adults with relapsing multiple sclerosis (RMS), according to a Novartis announcement.¹ The REMODEL-1 and REMODEL-2 data were presented in a late-breaking session at MSToronto2026 and published simultaneously in The Lancet.² The 100 mg dose lowered ARR by 35.2% and 31.2%, respectively.¹

Remibrutinib is a highly selective, covalent, oral BTK inhibitor discovered at Novartis.¹ The company plans to seek regulatory approval for the agent in RMS globally.¹ A 25 mg formulation (Rhapsido) is approved for chronic spontaneous urticaria in the US and the European Union.

“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,” Heinz Wiendl, MD, professor of neurology and chair of the Department of Neurology and Neurophysiology at the Medical Center, University of Freiburg, said in a statement.¹ “As treatment goals in MS continue to evolve beyond relapse control alone, 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.”

Remibrutinib efficacy in the phase 3 REMODEL-1 and REMODEL-2 trials

REMODEL-1 (NCT05147220) and REMODEL-2 (NCT05156281) are identical, multicenter, randomized, double-blind, active-comparator phase 3 trials in adults with RMS.¹ Investigators randomized 2007 patients globally, 1:1, to remibrutinib 100 mg or teriflunomide, which served as the active comparator. Eligible patients had recent disease activity and Expanded Disability Status Scale scores of 0.0 to 5.5.¹

The double-blind core part lasts up to 30 months, followed by an open-label extension of up to 5 years. ARR was the primary end point. Key secondary end points included 3-month and 6-month confirmed disability progression (CDP), new or enlarging T2 lesions per year, gadolinium-enhancing (Gd+) T1 lesions per scan, serum neurofilament light chain (sNfL), and no evidence of disease activity (NEDA-3).

In REMODEL-1, ARR was 0.073 with remibrutinib vs 0.112 (rate ratio [RR] 0·648 [95% CI 0·453–0·927]; p=0·018) with teriflunomide, a 35.2% relative reduction. In REMODEL-2, ARR was 0.080 vs 0.116 (RR 0·688 [0·487–0·972]; p=0·034), a 31.2% relative reduction. Novartis said the reductions equate to about 1 relapse every 13 years.¹

Remibrutinib secondary end points and safety versus teriflunomide

Remibrutinib lowered the risk of 6-month CDP by 29.2% (nominal significance) and the risk of 3-month CDP by 20.5%, according to the company. Over 24 months, more than 92% of patients treated with remibrutinib remained free of 6-month CDP.¹ Pooled analyses showed approximately 3 times higher odds of overall disease control with remibrutinib.¹

MRI outcomes favored remibrutinib in both trials. Annualized T2 lesion activity was 0.94 vs 2.71 in REMODEL-1 and 0.82 vs 2.77 in REMODEL-2, and Gd+ T1 lesions per scan were 0.08 vs 0.24 and 0.07 vs 0.21, respectively. Serum NfL improved by 9.0% and 7.0% vs teriflunomide, and the pooled NEDA-3 rate was 55.0% vs 32.1%.¹

No liver safety signal emerged, and investigators reported no Hy's Law cases. Alanine aminotransferase above 3 times the upper limit of normal occurred in 2.0% of patients treated with remibrutinib vs 7.4% with teriflunomide. In pooled analyses, discontinuations due to adverse events were 3.1% vs 5.8%.¹

Any adverse event occurred in 79.5% vs 81.5% of patients, and serious adverse events in 6.0% vs 7.0%. Two deaths occurred in the remibrutinib group, and investigators judged both unrelated to treatment.¹

The 100 mg dose studied in REMODEL is higher than the 25 mg dose approved for chronic spontaneous urticaria. Remibrutinib is also under investigation in secondary progressive MS in the REMASTER trial (NCT07225504), as well as in hidradenitis suppurativa and food allergy. Rhapsido received FDA approval for symptomatic dermographism in October 2026.¹

Previously, novartis announced that its oral investigational remibrutinib met the primary end point in the phase 3 REMODEL-1 and REMODEL-2 trials, significantly reducing annualized relapse rate (ARR) compared with teriflunomide.³ 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.

References
1. Novartis remibrutinib delivered comprehensive disease control in Phase III RMS trials, with proven, robust safety profile. Novartis. News release. Published October 23, 2026. Accessed October 23, 2026. https://www.globenewswire.com/news-release/2026/10/23/3387514/0/en/novartis-remibrutinib-delivered-comprehensive-disease-control-in-phase-iii-rms-trials-with-proven-robust-safety-profile.html
2. 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. Lancet. 2026; 0. Doi: 10.1016/S0140-6736(26)02058-1
3. 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