NEW YORK — For most of the nearly one million Americans living with relapsing multiple sclerosis, the treatment conversation with a neurologist follows a familiar arc. The high-efficacy drugs that meaningfully reduce relapses mostly require infusions or injections, a sustained clinical commitment not every patient can manage. The oral alternatives are effective, but they work at a lower ceiling. That gap between those two options has been the most consequential unresolved problem in MS medicine for years.
On September 1, Novartis announced results that could change the shape of that gap. Remibrutinib, a once-daily oral pill already approved in the United States and European Union for chronic spontaneous urticaria, a debilitating inflammatory skin condition, met its primary endpoint in two large Phase III trials for relapsing MS, in its announcement. The drug beat teriflunomide, a widely prescribed oral therapy used as the standard-of-care comparator, at reducing the annualized relapse rate. The results came from the REMODEL-1 and REMODEL-2 trials, each enrolling roughly one thousand patients and running up to thirty months.
Novartis has not yet released the exact percentage reduction in relapses, holding that data for a late-breaking presentation at the MSToronto2026 neurology conference next month. What the company did disclose, and what neurologists following the BTK inhibitor class are scrutinizing most closely, is the drug’s safety profile. Remibrutinib showed no liver safety signal in either trial.
That detail carries outsized weight right now. Tolebrutinib, a rival BTK inhibitor developed by Sanofi, was declined by the FDA earlier this year in its current form after regulators cited liver toxicity concerns. The absence of a liver signal also has implications for how patients would be monitored in practice. Liver toxicity concerns in clinical trials typically translate into required periodic blood testing and hepatic monitoring for patients on approved therapy, adding clinic visits and complexity to what was supposed to be a simpler oral regimen. If remibrutinib’s clean liver profile holds through full FDA review, it would spare patients that monitoring burden.
BTK (Bruton’s tyrosine kinase) is an enzyme that governs how B cells and certain innate immune cells respond to activation signals. In relapsing MS, those cells drive the neuroinflammation that gradually strips the myelin sheath from nerve fibers, producing the relapses, fatigue, and progressive disability that define the disease. By blocking BTK with the precision a covalent inhibitor allows, remibrutinib interrupts that inflammatory cascade at a level of cellular specificity that older oral MS drugs did not target directly.
BTK inhibition in MS is part of a broader shift toward targeting neurological diseases at the level of cell signaling, a shift that has also yielded progress in neurological gene therapy for conditions like Huntington’s disease. Remibrutinib brings that same precision-targeting philosophy to the autoimmune side of neurological medicine, applying to the central nervous system the same mechanism that earned it its first regulatory approval.
The REMODEL trials, registered in the federal clinical trial registry as NCT05147220 and NCT05156281, achieved superiority over teriflunomide across all key secondary endpoints in each individual study, including reductions in new and enlarging MRI lesions. On disability progression, the metric patients and families track most closely, the data are more nuanced. Three-month confirmed disability progression showed a positive trend. A pre-planned combined analysis of both trials found the six-month measure nominally statistically significant. The complete disability dataset will receive fuller scrutiny when Novartis presents at MSToronto2026.
What the trials leave open is how remibrutinib compares to the most potent MS drugs in current use. Agents like natalizumab and ocrelizumab reduce relapses by considerably larger margins than teriflunomide but require regular infusions. Until a head-to-head against those injectable high-efficacy therapies is conducted or real-world data emerges, the drug’s position in the treatment hierarchy for newly diagnosed patients remains an open clinical question.
The importance of oral therapy in MS is not simply about convenience. Research has consistently found that patients on injectable or infusion-based high-efficacy therapies achieve better long-term disability outcomes than those on lower-efficacy oral agents. It has also found that a meaningful proportion of those patients discontinue infusion-based treatment within the first two years, often because of the logistical and psychological burden of regular clinic visits. An oral drug that closes the efficacy gap without the liver risk that excluded a predecessor could represent a structural shift in how neurologists approach treatment decisions for newly diagnosed patients weighing a decades-long commitment.
Remibrutinib is not entering an empty class. Roche announced earlier this year that fenebrutinib, its BTK inhibitor, met its primary endpoint in Phase III trials for relapsing MS and showed activity in primary progressive MS, a form of the disease with even fewer approved therapies. Two large positive BTK datasets in a single year confirm that blocking BTK in MS is scientifically sound. Remibrutinib’s clean safety profile, if it holds through regulatory review, may determine which compound reaches the clinic first and for the broadest patient population.
Novartis plans to present full REMODEL trial results at MSToronto2026 before submitting to health authorities globally.
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