Novartis Remibrutinib Shows Strong Phase 3 Results in Multiple Sclerosis

Novartis’ oral Bruton’s tyrosine kinase (BTK) inhibitor remibrutinib met the primary endpoint in both Phase III REMODEL-1 and REMODEL-2 trials, demonstrating a statistically significant reduction in annualized relapse rate (ARR) versus teriflunomide in adults with relapsing multiple sclerosis (RMS).

The results position remibrutinib as a potential oral high-efficacy treatment for RMS, with additional benefits observed across MRI measures of inflammatory disease activity and disability progression.

Remibrutinib Delivers Broad Efficacy Across REMODEL Trials

Both trials showed superiority over teriflunomide across key secondary endpoints, including reductions in new or enlarging T2 lesions and gadolinium-enhancing T1 lesions, which reflect inflammatory activity in the central nervous system.

A preplanned pooled analysis of REMODEL-1 (NCT05147220) and REMODEL-2 (NCT05156281) also showed a clinically meaningful delay in disability progression. The analysis demonstrated a positive trend for 3-month confirmed disability progression (3mCDP), while 6-month confirmed disability progression (6mCDP) reached nominal statistical significance.

The findings are important because RMS treatment extends beyond preventing clinical relapses. Persistent inflammatory activity can contribute to accumulating neurological damage and disability, making control of both overt and subclinical disease activity a key treatment goal.

The trials also evaluated serum neurofilament light chain (sNfL) concentrations and no evidence of disease activity (NEDA-3), among other secondary measures.

Selective BTK Inhibition Targets Multiple Immune Pathways

Remibrutinib is a highly selective oral BTK inhibitor discovered by Novartis. By blocking BTK signaling, the drug reduces activation of B cells and innate immune cells involved in immune regulation and neuroinflammation.

The approach is particularly relevant to MS because both adaptive and innate immune mechanisms contribute to inflammatory injury within the central nervous system.

Remibrutinib is already approved as Rhapsido in the US and European Union for adults with chronic spontaneous urticaria, providing a broader clinical safety experience. Its development continues across neurological and immune-mediated diseases.

Favorable Safety Profile with No Liver Safety Signal

Safety results from REMODEL-1 and REMODEL-2 remained consistent with the broader remibrutinib development program, which includes more than 4,500 clinical trial participants across multiple indications.

Novartis reported that remibrutinib was well tolerated and that the trials identified no liver safety signal. No cases meeting Hy’s Law criteria were reported.

This safety finding is notable given the importance of hepatic monitoring in the development of several BTK inhibitors and strengthens the drug’s potential benefit-risk profile if the efficacy findings translate into long-term clinical benefit.

Data to Be Presented at MSToronto2026

Shreeram Aradhye, President, Development, and Chief Medical Officer at Novartis, said the REMODEL findings address the need for oral therapies that combine relapse prevention with slowing disability progression while maintaining favorable tolerability.

The company plans to present detailed REMODEL-1 and REMODEL-2 data as late-breaking results at MSToronto2026. Novartis also intends to hold an investor call after the congress presentation.

Following the full data disclosure, the company plans to seek regulatory approval for remibrutinib in RMS across global markets. The Phase III program includes approximately 2,000 patients randomized 1:1 to remibrutinib 100 mg or teriflunomide, with a double-blind core period lasting up to 30 months and an open-label extension of up to five years.

 Reference

Novartis remibrutinib, a high-efficacy oral BTK inhibitor, significantly reduces relapse rates and shows favorable safety profile in Phase III RMS trials | Novartis