Remibrutinib beat an older oral drug on relapses in multiple sclerosis

Remibrutinib, an oral drug that blocks Bruton's tyrosine kinase (BTK), reduced relapses in people with relapsing multiple sclerosis more than teriflunomide, an established oral therapy, in two large phase 3 trials published together in The Lancet [s1]. It is a genuine positive result on the trials' main measure. What it does not yet show is whether the drug slows the disability that makes multiple sclerosis feared — and the comparator it beat is not the strongest available.

Multiple sclerosis is an immune-mediated disease in which the body attacks the insulating myelin around nerves, producing relapses — discrete attacks of neurological symptoms — and, over years, accumulating disability. BTK inhibitors are a newer class that act inside both B cells and the brain's own immune cells, and remibrutinib is described by the investigators as highly selective, covalent and able to cross into the central nervous system [s1]. The pitch is an oral alternative to the infused antibody therapies that dominate high-efficacy treatment.

What the trials did

REMODEL-1 and REMODEL-2 were two identical, double-blind, double-dummy, event-driven phase 3 trials run at 407 centres in 46 countries, registered as NCT05147220 and NCT05156281 [s1][s2][s3]. Adults aged 18–55 with relapsing multiple sclerosis, recent disease activity and an Expanded Disability Status Scale score of 0–5.5 were randomly assigned 1:1 to oral remibrutinib 100 mg twice daily or teriflunomide 14 mg once daily [s1]. The primary endpoint was the annualised relapse rate (ARR) — the number of confirmed relapses per patient-year — over up to 30 months of follow-up [s1]. Running two identical trials is deliberate: a result that replicates across both is far harder to dismiss as chance than a single trial's finding.

Between December 2021 and December 2025 the trials randomly assigned 2,007 patients in total — 1,000 in REMODEL-1 and 1,007 in REMODEL-2 — split evenly between the two drugs [s1]. About two-thirds of participants were women, consistent with the disease's epidemiology, and the trials were ongoing but no longer recruiting at the time of this analysis [s1].

Teriflunomide was chosen as the comparator rather than a placebo for an ethical reason worth naming: withholding any active treatment from people with active relapsing disease over two-and-a-half years would be hard to justify. That makes the trials a test of relative benefit against a known drug, not of benefit against nothing — a design that is standard in this field but shapes how the numbers should be read.

What it found

In REMODEL-1 the annualised relapse rate was 0.073 on remibrutinib versus 0.112 on teriflunomide (rate ratio 0.648, 95% CI 0.453–0.927; p=0.018) [s1]. REMODEL-2 reproduced the pattern almost exactly: 0.080 versus 0.116 (rate ratio 0.688, 0.487–0.972; p=0.034) [s1]. In both trials that works out to roughly a third fewer relapses, and the replication across two separate trials is the result's real strength.

Safety looked reassuring on the numbers reported. The most common adverse events — upper respiratory infections, nasopharyngitis, diarrhoea and hair loss — were similar to or less frequent than with teriflunomide, and discontinuations because of adverse events were lower on remibrutinib (3.1% versus 5.8%) [s1]. The investigators reported no liver safety concerns, a point that matters because an earlier drug in this class, evobrutinib, was set back by liver toxicity [s1].

How to read it

Two things temper the enthusiasm. First, the comparator. Teriflunomide is a real, approved therapy, but it sits at the modest end of efficacy; beating it is a lower bar than matching or beating the high-efficacy antibody drugs many patients with active disease now start on. These trials do not tell you how remibrutinib stacks up against those. Second, and more important, relapse rate is not the endpoint patients and neurologists care about most. Disability progression — the slow, often relapse-independent worsening that BTK inhibitors are specifically hoped to address — is reported as a secondary outcome here, and the headline relapse win does not by itself establish a disability benefit [s1]. The trials were funded by Novartis, the drug's maker [s1].

What it means

Remibrutinib now has consistent, replicated phase 3 evidence that it lowers relapses more than teriflunomide, which is likely enough to support regulatory filings. Whether it earns a place as a high-efficacy oral option will depend on the disability data, on longer-term safety as more patients accumulate exposure, and on head-to-head comparisons the field still lacks. For now the accurate summary is specific: fewer relapses than an older oral drug, proven twice — not yet proof that the disease's long arc is being bent.