NEW ORLEANS—Ublituximab, a novel glycoengineered anti-CD20 antibody, is well tolerated and demonstrates rapid and robust B-cell depletion, according to a report presented at the 31st Annual Meeting of the Consortium of Multiple Sclerosis Centers. “Unlike other anti-CD20s, ublituximab can be delivered in shorter infusions, providing a convenience benefit for patients,” reported Amy Lovett-Racke, PhD, and her research colleagues. Dr. Lovett-Racke is a Professor in the Department of Microbial Infection and Immunity at Ohio State University Medical Center in Columbus.
Amy Lovett-Racke, PhD
Patients with relapsing or primary progressive forms of multiple sclerosis (MS) have shown significant clinical improvement after B-cell depletion with an anti-CD20 antibody. Ublituximab is a chimeric monoclonal antibody that targets a unique epitope on the CD20 antigen. It has been glycoengineered to enhance affinity for all variants of FcgRIIIa receptors, demonstrating greater antibody-dependent cellular cytotoxicity (ADCC) activity than rituximab. Ublituximab is currently in phase III trials for the treatment of hematologic malignancies.
To determine the level of B-cell depletion by ublituximab in subjects with relapsing MS, Dr. Lovett-Racke and colleagues conducted a 52-week, phase II, placebo-controlled, multicenter study that was designed to assess the infusion time and optimal dose as well as the safety and tolerability of ublituximab in patients with relapsing MS. The investigators also performed radiologic and clinical analyses. Optimal dosing was determined by B-cell depletion, defined as percentage of CD19+ B cells present following ublituximab administration. This percentage was calculated by gating the entire lymphocyte/myeloid population. Within this population, CD19+ CD3− cells were gated, and the percentage of CD19+ B cells was determined.
To date, B-cell data from 11 subjects have been analyzed up to week four of the 52-week study, encompassing two infusions of ublituximab. No severe adverse events have been reported, including in subjects receiving rapid infusions. Only patients whose B-cell levels were within a normal range (≥ 5% of total lymphocytes) at screening were included in the study. At week four (one week post second infusion), median B-cell depletion was 99% from baseline in ublituximab-treated subjects, while controls maintained similar B-cell levels, as compared with baseline.
This study was supported by TG Therapeutics.