Relapse Rates Drop Significantly in Relapsing Multiple Sclerosis Trial

ORAL remibrutinib demonstrates significant relapse reduction compared with teriflunomide in relapsing multiple sclerosis across twin Phase 3 trials. The twin international studies, REMODEL-1 and REMODEL-2, evaluated the highly selective, central nervous system-penetrant Bruton tyrosine kinase inhibitor in over two thousand adult participants presenting with active relapsing forms of the disease. In contrast to anti-CD20 monoclonal antibody infusions that trigger continuous B-cell clearance, the investigational oral agent targets acute and compartmentalized inflammation by inhibiting Bruton tyrosine kinase enzymatic signaling in B cells and microglia without depleting circulating immune cells.

Investigators randomly assigned participants to receive either remibrutinib one hundred milligrams twice daily or oral teriflunomide fourteen milligrams once daily for up to thirty months of double-blind therapy. In REMODEL-1, the annualized relapse rate was 0.073 with the kinase inhibitor versus 0.112 with teriflunomide, representing a 35.2 percent relative risk reduction. In REMODEL-2, annualized relapse rates reached 0.080 and 0.116, respectively, reflecting a 31.2 percent reduction. This disease control equates mathematically to an estimated single clinical relapse every thirteen years under sustained oral treatment.

Neuroimaging Outcomes and Safety in Relapsing Multiple Sclerosis

Neuroimaging endpoints exhibited marked reductions in objective measures of acute and chronic neuroinflammation throughout both trials. New or enlarging annualized T2 lesion activity dropped by 65 percent in REMODEL-1 and 70 percent in REMODEL-2 compared with the active control. Gadolinium-enhancing T1 lesions on serial magnetic resonance imaging scans showed a 66 percent decrease in both trials. Exploratory analyses also demonstrated a 29.2 percent reduction in confirmed disability progression sustained at six months.

The safety profile remained favorable and addressed primary hepatotoxicity concerns associated with earlier generation kinase inhibitors in neurology. Treatment discontinuations due to adverse events occurred in 3.1 percent of remibrutinib recipients compared with 5.8 percent of those on teriflunomide. No Hy’s Law cases occurred, and elevated liver enzymes occurred at lower rates than seen with the active comparator. Common adverse events consisted predominantly of mild upper respiratory tract infections and nasopharyngitis. These findings suggest selective oral enzymatic blockade represents a viable option for managing relapsing multiple sclerosis.

Reference

Wiendl H et al. Remibrutinib versus teriflunomide in relapsing multiple sclerosis (REMODEL-1 and REMODEL-2): two randomised, phase 3 trials. Lancet. 2026; doi: 10.1016/S0140-6736(26)02058-1.