Remibrutinib Relapsing Multiple Sclerosis: REMODEL Trials Cut Relapse Rates

Novartis’ oral BTK inhibitor remibrutinib has cleared a major Phase III test in relapsing multiple sclerosis (RMS). The remibrutinib relapsing multiple sclerosis program reported a significantly lower annualized relapse rate (ARR) than teriflunomide in the REMODEL-1 and REMODEL-2 trials, along with a favorable safety profile. The result moves a high-efficacy oral toward a market that still leans heavily on older, now-generic therapies.

Remibrutinib relapsing multiple sclerosis trial results

REMODEL-1 and REMODEL-2 are identical multicenter, randomized, double-blind studies that compared remibrutinib 100 mg with teriflunomide in adults with RMS. Roughly 2,000 patients with recent disease activity and an Expanded Disability Status Scale (EDSS) score of 0.0 to 5.5 were randomized 1:1. The primary endpoint was annualized relapse rate.

Both trials met that endpoint. Remibrutinib also outperformed teriflunomide on every key secondary endpoint within each trial, including the number of new or enlarging T2 lesions and gadolinium-enhancing T1 lesions on MRI. On disability progression, a preplanned combined analysis of the two studies showed a positive trend in three-month confirmed disability progression (3mCDP) and nominal significance in six-month confirmed disability progression (6mCDP).

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The studies run a double-blind core part of up to 30 months, then an open-label extension of up to five years. Secondary endpoints also cover serum neurofilament light chain (sNfL) concentration and the share of participants with no evidence of disease activity (NEDA-3).

Safety profile

Safety in REMODEL-1 and REMODEL-2 matched the wider remibrutinib development program, which spans more than 4,500 trial participants across several indications. The drug was well tolerated and continues to show no liver safety signal, including no cases meeting Hy’s Law criteria. That record matters in MS, where liver monitoring is a routine burden for several existing disease-modifying therapies.

Market access implications

Multiple sclerosis affects nearly 3 million people worldwide, and relapsing MS is its most common form. The relapsing MS market is crowded with generics and biosimilars, but it still lacks oral options that pair high efficacy with a clean liver profile. Teriflunomide, the active comparator here, is itself a first-line oral whose patents have lapsed, so remibrutinib’s case to payers will rest on the size of its ARR advantage and the disability progression signal rather than on novelty alone.

Delaying confirmed disability progression is the endpoint that matters most for long-term cost. In MS, most lifetime healthcare and indirect costs track accumulating disability, so a 6mCDP benefit carries direct health economic weight. The cost-effectiveness of disease-modifying therapies in relapsing-remitting MS has been studied at length, and recent health technology assessment decisions in MS, from NICE’s natalizumab expansion to Portugal’s funding of Briumvi, show how payers now gatekeep newer therapies.

“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. 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,” said Shreeram Aradhye, President, Development, and Chief Medical Officer, Novartis.

Novartis presents both studies as a late-breaker at MSToronto2026 and plans to submit for regulatory approval in RMS globally. If the final data hold up, payers will weigh remibrutinib against the established efficacy of existing orals and the monitoring convenience its safety record implies.

About remibrutinib

Remibrutinib is a highly selective oral Bruton’s tyrosine kinase (BTK) inhibitor that blocks the BTK pathway, reducing activation of B cells and innate immune cells to modulate neuroinflammation. Novartis is studying it in neuroscience indications including the REMODEL trials in RMS and the REMASTER trial in secondary progressive MS, as well as in hidradenitis suppurativa and food allergy. Remibrutinib 25 mg is already approved as Rhapsido for chronic spontaneous urticaria, with FDA clearance in September 2025 and European Commission approval in April 2026.