Remibrutinib versus teriflunomide in relapsing multiple sclerosis (REMODEL-1 and REMODEL-2): two randomised, phase 3 trials.

October 23, 2026| Source: Lancet (London, England)

Remibrutinib is a highly selective, potent, covalent, CNS-penetrant, oral BTK inhibitor. We assessed the efficacy and safety of remibrutinib in adult patients with relapsing multiple sclerosis. REMODEL-1 and REMODEL-2 are two identical, randomised, double-blind, double-dummy, active comparator-controlled, parallel-group, event-driven, phase 3 trials conducted at 407 centres in 46 countries. Patients aged 18-55 years with relapsing multiple sclerosis, an Expanded Disability Status Scale score of 0-5·5, and evidence of recent disease activity were randomly assigned 1:1 to oral remibrutinib 100 mg twice daily or teriflunomide 14 mg once daily via interactive response technology. Randomisation was stratified by geographical region, MRI cohort participation, and multiple sclerosis subtype. Patients, site investigators, and trial team were masked to treatment allocation. The primary endpoint was annualised relapse rate (ARR), defined as the number of confirmed multiple sclerosis relapses per patient-year with up to 30 months of follow-up, and assessed in all randomly assigned patients. These trials are registered with ClinicalTrials.gov (NCT05147220 and NCT05156281) and are ongoing, not recruiting. Between Dec 13, 2021, and Dec 30, 2025, 2632 patients were screened and 2007 patients were randomly assigned. REMODEL-1 included 1000 patients (remibrutinib 502, teriflunomide 498; mean age 38·2 years, 666 [66·6%] female, 334 [33·4%] male) and REMODEL-2 included 1007 patients (remibrutinib 504, teriflunomide 503; mean age 39·0 years, 675 [67·0%] female, 332 [33·0%] male). ARR was significantly lower with remibrutinib than with teriflunomide: 0·073 versus 0·112 (rate ratio [RR] 0·648 [95% CI 0·453-0·927]; p=0·018) in REMODEL-1 and 0·080 versus 0·116 (RR 0·688 [0·487-0·972]; p=0·034) in REMODEL-2. The most common adverse events were upper respiratory tract infection (132 [13·1%] of 1006 with remibrutinib vs 137 [13·7%] of 1001 with teriflunomide), nasopharyngitis (92 [9·1%] vs 123 [12·3%]), diarrhoea (84 [8·3%] vs 109 [10·9%]), and alopecia (58 [5·8%] vs 135 [13·5%]). Adverse events leading to treatment discontinuation were less frequent with remibrutinib (31 [3·1%]) versus teriflunomide (58 [5·8%]). The safety profile of remibrutinib was consistent with that in other indications, including no liver safety concerns. Remibrutinib was superior to teriflunomide in patients with relapsing multiple sclerosis, while maintaining a favourable safety profile. These findings support remibrutinib as a potential new oral treatment option for relapsing multiple sclerosis. Novartis.

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