Novartis has announced positive topline results from the Phase III REMODEL-1 and REMODEL-2 trials evaluating remibrutinib, an oral Bruton’s tyrosine kinase (BTK) inhibitor, in adults with relapsing multiple sclerosis (RMS).
The investigational therapy met the primary endpoint in both trials, demonstrating a statistically significant reduction in annualized relapse rate (ARR) compared with teriflunomide. The studies also reported favorable results across key secondary endpoints, including measures of inflammatory brain lesions seen on MRI.
According to Novartis, remibrutinib demonstrated superiority over teriflunomide on the key secondary endpoints evaluated in each REMODEL study. The treatment was associated with reductions in new or enlarging MRI lesions, highlighting its potential to reduce inflammatory disease activity in people living with RMS.
A preplanned combined analysis of REMODEL-1 and REMODEL-2 also showed a positive trend in 3-month confirmed disability progression (3mCDP), while 6-month confirmed disability progression (6mCDP) reached nominal statistical significance. These findings indicate a clinically meaningful potential delay in disability progression.
Novartis reported that remibrutinib was generally well tolerated in the two Phase III studies. Importantly, the company said there was no liver safety signal, including no cases meeting Hy’s Law criteria.
The safety findings were described as consistent with the broader remibrutinib clinical development program, which has included more than 4,500 clinical trial participants across multiple indications.
Remibrutinib is a highly selective oral BTK inhibitor designed to block the BTK pathway. By modulating the activity of B cells and innate immune cells, the drug is intended to influence immune regulatory pathways involved in inflammation and neuroinflammation.
The compound is being studied in several immune-mediated and neurological conditions, including RMS and secondary progressive multiple sclerosis (SPMS). Remibrutinib is already approved under the brand name Rhapsido for chronic spontaneous urticaria in the United States and European Union.
REMODEL-1 and REMODEL-2 are multicenter, randomized, double-blind, active-comparator Phase III studies comparing remibrutinib with teriflunomide in adults with RMS.
Approximately 2,000 participants globally were randomized to receive either remibrutinib 100 mg or teriflunomide. The primary endpoint was annualized relapse rate, while secondary measures included confirmed disability progression, MRI lesion activity, serum neurofilament light chain levels and no evidence of disease activity (NEDA-3).
Novartis plans to present detailed results from REMODEL-1 and REMODEL-2 as late-breaking data at MSToronto2026. The company also intends to seek regulatory approval for remibrutinib for RMS in markets worldwide.
The Phase III findings could potentially strengthen the role of oral BTK inhibition as an approach to managing relapsing multiple sclerosis, although regulatory review and approval will be required before remibrutinib can be used for RMS.
