Evobrutinib nonsuperior to teriflunomide for relapsing forms of MS

Key takeaways:

• Permanent discontinuation due to treatment-emergent adverse events occurred in 12% and 10.6% of treatment groups.
• Researchers called the results “disappointing.”

WEST PALM BEACH, Fla. — Treatment with evobrutinib was nonsuperior to teriflunomide in confirmed disability progression at 12 and 24 weeks for those with relapsing forms of multiple sclerosis, according to a presenter at ACTRIMS 2024.

“In a phase 3 trial several years ago, we showed that evobrutinib 75 mg twice per day, taken fasted, had the best ... profile compared to the other standing doses,” Xavier Montalban, MD, PhD, chair of the department of neurology at Vall d’Hebron University Hospital in Barcelona, Spain, told attendees.

Montalban and colleagues sought to investigate the safety and efficacy of evobrutinib, an investigational, oral, central nervous system-penetrant and highly selective Bruton’s tyrosine kinase inhibitor. compared with teriflunomide in those with relapsing forms of MS

EvolutionRMS 1 and 2 were multicenter, randomized, double-blind, double-dummy, controlled trials conducted across 52 countries between July 2020 and November 2022. From an initial screened cohort of more than 3,000 persons, they included more than 2,000 individuals (evolutionRMS 1, n = 1,124; evolutionRMS 2, n = 1,166) diagnosed with active relapsing-remitting or active secondary progressive MS and an Expanded Disability Status Scale (EDSS) score of 0 to 5.5, who were deemed neurologically stable at least 30 days prior to baseline. All were randomized 1:1 to receive either 45 mg evobrutinib twice daily or 14 mg teriflunomide once daily, both taken with food.

The study’s primary endpoint was annualized relapse rate and was assessed over a variable treatment duration per patient (minimum for 24 weeks and up to 156 weeks) in the double-blind treatment period. Secondary endpoints included time to confirmed disability progression (CDP) or improvement outcomes at 12-week and 24-week intervals, along with safety and tolerability profiles.

According to results, 12-week CDP in evobrutinib was 11.9% and 13% for teriflunomide, with 24-week CDP at 7.7% and 7.1%, respectively.

Treatment-emergent adverse events (TEAEs) occurred in 85.6% of those treated with evobrutinib and 87.2% of those given teriflunomide, with the most common being COVID-19 infection, headache and increase of alanine aminotransferase. Permanent discontinuation due to TEAEs occurred in 12% and 10.6% of treatment groups, respectively.

“These results were quite disappointing for all of us,” Montalban said. “And, in fact, they were devastating for patients, their families, for investigators and for the Merck people.”