Novartis remibrutinib meets Phase III endpoints in relapsing MS
Novartis has reported positive topline results from its twin Phase III REMODEL-1 and REMODEL-2 trials of remibrutinib in adults with relapsing multiple sclerosis (RMS), saying both studies met their primary endpoint of reducing annualised relapse rate (ARR) compared with the active comparator teriflunomide.
The trials enrolled approximately 2,000 patients globally in a 1:1 randomised, double-blind design, comparing remibrutinib 100 mg against teriflunomide across a core treatment period of up to 30 months. Both studies also achieved superiority on all key secondary endpoints within each trial, including reductions in new and enlarging MRI T2 lesions and gadolinium-enhancing T1 lesions.
Trial results and disability data
Disability progression outcomes, a harder bar to clear in RMS trials, were also favourable. A preplanned combined analysis of REMODEL-1 and REMODEL-2 showed a positive trend in three-month confirmed disability progression (3mCDP) and nominal statistical significance in six-month confirmed disability progression (6mCDP). The six-month measure is generally considered the more clinically meaningful of the two, and nominal significance in a preplanned combined analysis will attract scrutiny from regulators and clinicians who will want to see the full dataset.
Remibrutinib's safety profile was consistent with the broader development programme spanning more than 4,500 participants across multiple indications. Notably, no liver safety signal was observed and no cases met Hy's Law criteria, a threshold regulators use to identify drugs with potential for serious drug-induced liver injury. That finding differentiates remibrutinib from some earlier BTK inhibitors where hepatotoxicity was a concern in other therapeutic settings.
Shreeram Aradhye, president of development and chief medical officer at Novartis, said the results "underscore the potential of remibrutinib as a high-efficacy oral therapy for people living with RMS with a differentiated benefit-risk profile." Novartis plans to present full data as a late-breaker at MSToronto2026 and to follow with an investor call before initiating global regulatory submissions.
Market context and competitive positioning
The RMS treatment landscape is already densely populated. High-efficacy injectables and infusibles, including natalizumab, ocrelizumab and ofatumumab, set a high bar for relapse reduction. Among oral therapies, sphingosine-1-phosphate receptor modulators such as siponimod and ozanimod have broadened the oral high-efficacy segment, though liver monitoring requirements and cardiac effects have complicated prescribing for some patients. Cladribine and fumarates occupy different niches. Teriflunomide, the comparator chosen for the REMODEL trials, is an established but modest-efficacy oral agent, which means a superiority result against it, while commercially useful, does not yet answer how remibrutinib stacks up against the most potent anti-CD20 therapies.
The BTK inhibitor class is attracting significant interest in neuroinflammation. Tolebrutinib from Sanofi, which received FDA approval for non-relapsing secondary progressive MS in mid-2025, is the reference point the market will use most immediately. Sanofi's programme had its own liver safety concerns, resulting in a label warning, so Novartis's clean hepatic profile data could prove a meaningful differentiator if it holds at regulatory review.
Remibrutinib is already approved as Rhapsido for chronic spontaneous urticaria by both the FDA (September 2025) and EMA (April 2026), giving the molecule an established commercial and regulatory track record that should smooth the path for the MS filing. Novartis also has REMASTER, a Phase III trial in secondary progressive MS, still running, meaning additional label breadth may follow in subsequent years.
Full data presentation at MSToronto2026 will be the next critical moment, with the hazard ratios, absolute ARR values, and complete safety tables needed before analysts and neurologists can fully assess where remibrutinib sits in the treatment hierarchy.