Evobrutinib Reduces Relapsing Multiple Sclerosis Disease Activity

Post-hoc analysis of data from a phase 2 study (NCT02975349) of evobrutinib (M2951; EMD Serono, Rockland, MA) reduced the volume of slowly expanding MRI lesions in participants with relapsing multiple sclerosis (MS). Slowly expanding lesions are chronic, active areas of demyelination thought to predict disease progression in relapsing MS. Evobrutinib reduced volume of this lesion type a dose-dependent manner compared with placebo, with the highest effect with 75 mg twice daily (P=0.047). Participants treated with evobrutinib 75 mg once or twice daily also had reduced MRI lesion activity and relapse outcomes vs placebo or evobrutinib 25mg once daily. 

“The presented analysis is the first to show a BTK inhibitor significantly reducing slowly expanding lesion volume in patients with relapsing MS, providing further evidence to support the mechanism of action of evobrutinib in the treatment of RMS and underscoring the molecule’s potential impact on neurodegeneration and disease progression,” said  Xavier Montalban, MD, PhD, chairman and director, Multiple Sclerosis Centre of Catalonia, Vall d'Hebron University Hospital. 

Evobrutinib was generally well-tolerated with similar rates of adverse events between evobrutinib and placebo by indication and across trials. The most common adverse events reported were urinary tract infections (9.5% versus 8.5% placebo), nasopharyngitis (7.3% versus 5.5% placebo), diarrhea (6.2% versus 4.8% placebo) and alanine aminotransferase increase (2.9% versus 1.5% placebo). Liver transaminase elevations were asymptomatic and reversible upon treatment discontinuation.

Evobrutinib is an orally administered central nervous system (CNS)-penetrant Bruton tyrosine kinase inihibitor (BTKi) designed to inhibit primary B-cell responses such as proliferation and antibody and cytokine release without directly affecting T-cells. With these results, evobrutinib is the first in this drug class to show an effect on slowly expanding lesions in MS. 

These data were presented at the European Congress on Advances in Treatment of Multiple Sclerosis, held online from October 13-15, 2021.