Ublituximab: A Novel Anti-CD20 Therapy for Multiple Sclerosis

Ublituximab is a novel anti-CD20 therapy developed for the treatment of patients with multiple sclerosis. It is a glycoengineered chimeric antibody with a novel epitope on CD20, with high antibody-dependent cell-mediated cytotoxicity. Maintenance doses are administered every 6 months over an hour, providing a convenient dosing regimen. The identical phase III randomized, double-blind, active comparator to teriflunomide trials ULTIMATE I and II were completed in early 2022. ULTIMATE I and II, respectively, demonstrated that ublituximab had a strong clinical effect, with annualized relapse rates of 0.08 and 0.09 or reductions of 59% and 49% over teriflunomide. In addition, in ULTIMATE I and II, radiographic efficacy similarly reduced contrast-enhancing lesions by 97% and 96% and new/enlarging T2 lesions by 92% and 90%, respectively. Although ublituximab did not decrease confirmed disability progression in a pooled analysis of both studies, there was an increase in the confirmed disability improvement. Ublituximab was well tolerated, including infusion reactions that were predominantly mild and only seen with the first infusion. Further long-term safety data, as well as relative efficacy compared with current anti-CD20 therapies, will need to be evaluated in the real-world setting if ublituximab is to be approved as expected in December 2022.