Novartis breaks BTK losing streak in multiple sclerosis
Novartis’ remibrutinib has beaten teriflunomide in two Phase 3 trials in relapsing multiple sclerosis (MS), adding another important clinical win for a class of BTK inhibitors that has endured several high-profile failures in autoimmune disease.
Why it matters: Bruton’s tyrosine kinase (BTK) inhibitors are best established as blood cancer drugs, but drugmakers have increasingly tried to use the same target to control overactive immune responses in autoimmune diseases.
- The transition has not been straightforward. Several candidates have failed pivotal trials, particularly in multiple sclerosis, while liver toxicity has complicated development of some drugs in the class.
Zoom in: The identical REMODEL-1 and REMODEL-2 trials enrolled about 2,000 adults with relapsing MS and compared oral remibrutinib with teriflunomide, an established oral disease-modifying therapy commonly used as an active comparator in late-stage MS trials.
- Novartis said both studies met their primary endpoint, with remibrutinib significantly reducing annualized relapse rates compared with teriflunomide. The drug also beat the comparator on all key secondary endpoints within each trial, including reducing inflammatory brain lesions.
- A pooled analysis showed a positive trend on three-month confirmed disability progression and a nominally significant benefit on six-month confirmed disability progression.
- The company has not yet disclosed the magnitude of the relapse reduction or detailed safety results. Full data will be presented at MSToronto2026 later this year.
How it works: BTK is involved in signaling in B cells as well as cells of the innate immune system. Blocking it offers a way to dampen several components of the immune response without directly depleting B cells, as treatments such as Roche’s Ocrevus and Novartis’ Kesimpta do. That biology has made BTK an attractive target well beyond oncology, including MS, urticaria, lupus and other inflammatory and autoimmune diseases.
- Remibrutinib has already validated that idea outside MS. Sold as Rhapsido, the drug was approved in the US in September 2025 and the EU in April for chronic spontaneous urticaria, making it the first oral BTK inhibitor approved for the condition.
Backstory: MS has been particularly unforgiving for the class. Germany’s Merck KGaA was once among the leaders with evobrutinib, but the drug failed to outperform teriflunomide on relapse rates in either of two Phase 3 EVOLUTION trials in 2023.
- Sanofi ran into the same problem with tolebrutinib. Its GEMINI 1 and 2 trials also failed to beat teriflunomide on relapse rates, although the drug subsequently showed a benefit on disability progression in non-relapsing secondary progressive MS and was subsequently approved in the EU.
- The class has nevertheless staged something of a comeback. Earlier this year, Roche reported that fenebrutinib reduced annualized relapse rates by 51% and 59% versus teriflunomide in two Phase 3 relapsing MS trials, while also producing positive Phase 3 results in primary progressive MS.
The safety question: Liver toxicity has been another recurring concern around BTK development in MS. That makes Novartis’ assertion that REMODEL produced no liver safety signal particularly important.
- The company said there were no cases meeting Hy’s Law criteria, a measure used to flag potentially serious drug-induced liver injury. Remibrutinib has now been studied in more than 4,500 clinical trial participants across indications.
What’s next: Novartis plans global regulatory submissions for remibrutinib in relapsing MS after presenting the detailed REMODEL data. The company is also testing the drug in Phase 3 in secondary progressive MS, as well as in other immune-mediated conditions including hidradenitis suppurativa and food allergy.
