Ublituximab Demonstrates Efficacy, Safety in Relapsing MS Over 6 Years

Early initiation of ublituximab demonstrates efficacy and a favorable safety profile through 6 years of treatment for relapsing multiple sclerosis (MS), according to study results presented at the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) Congress 2025, held in Barcelona, Spain from September 24 to 26, 2025.

The ULTIMATE I (ClinicalTrials.gov Identifier: NCT03277261) and ULTIMATE II (ClinicalTrials.gov Identifier: NCT03277248) phase 3 studies previously showed that ublituximab significantly reduced relapse rates over 2 years compared with teriflunomide. The current analysis extends these findings, reporting up to 6 years of follow-up, including 4 years of open-label extension.

Patients with relapsing MS who either remained on ublituximab throughout the study period (n=422) or switched from teriflunomide to ublituximab after 2 years (n=429) were included. Approximately 70% of patients completed year 6 from randomization.

Patients who switched from teriflunomide experienced a 58.5% reduction in annualized relapse rate after 1 year compared with those who remained on teriflunomide (0.182 vs 0.075; rate ratio, 0.415; 95% CI, 0.288-0.597; P <.0001). Annualized relapse rate continued to decline over time, reaching 0.032 by year 6. Among patients who received continuous ublituximab, relapse activity declined steadily across follow-up, with annualized relapse rate falling from 0.053 at year 3 to 0.012 by year 6, representing approximately 1 relapse every 83 years.

Disability outcomes also favored continuous treatment, with confirmed disability progression at year 6 occurring in 10.1% of patients compared with 15.9% of those who switched (hazard ratio [HR], 0.658; 95% CI, 0.457-0.948; P =.0238). Rates of confirmed disability improvement were also higher with continuous therapy compared with those who switched therapies (17.0% vs 13.3%, respectively; HR, 1.414; 95% CI, 1.015 to 1.970; P =.0396).

Immunoglobulin G and M levels remained above the lower limit of normal throughout continuous ublituximab treatment.

Treatment over the 6-year period was generally well tolerated, and no additional safety concerns emerged beyond what had already been established.

“Long term follow-up of [ublituximab]-treated participants from [open-label extension] confirmed the clinical benefits of early initiation of [ublituximab] on efficacy and safety,” the study authors concluded.

Disclosures: Multiple study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.