Rapid and Robust B Cell Depletion in Preliminary Results of a Phase 2 Study of Ublituximab, Novel Glycoengineered Anti-CD20 Mab, in RMS Patients

Background:  Patients with relapsing or primary progressive forms of multiple sclerosis have shown significant clinical improvement after B cell depletion with an anti-CD20 antibody.  Ublituximab (UTX) is a novel, chimeric mAb which targets a unique epitope on the CD20 antigen and has been glycoengineered to enhance affinity for all variants of FcγRIIIa receptors, demonstrating greater antibody-dependent cellular cytotoxicity activity (ADCC) than rituximab. UTX is currently in multiple phase III trials for treatment of hematologic malignancies.  

Objectives: To determine the level of B cell depletion by ublituximab in subjects with RMS

Methods: TG1101-RMS201 is a 52-week, phase 2, placebo-controlled, multicenter study that is designed to assess the infusion time and optimal dose as well as safety/tolerability of UTX in RMS subjects.  Radiological and clinical analysis are also performed.  Optimal dosing is determined by B cell depletion, defined as percentage of CD19⁺ B cells present following UTX administration. This is calculated by gating the entire lymphocyte/myeloid population.  Within this population, CD19⁺ CD3^- cells were gated and % CD19⁺B cells was determined.  

Results: To date, B cell data from 11 subjects have been analyzed up to week 4 of the 52-week study, encompassing two infusions of UTX.  Further, no SAEs have been reported, including subjects receiving rapid UTX infusions.  Only patients whose B cells were within a normal range (≥5% of total lymphocytes) at screening were included in the study. At week 4 (1 week post second infusion), median B cell depletion was 99% from baseline in UTX treated subjects, while placebo subjects maintained similar B cell levels as compared to baseline. [Data from ≥24 patients, will reported at the conference.]

Conclusions: Ublituximab, a novel glycoengineered anti-CD20 antibody, is well tolerated and demonstrates rapid and robust B cell depletion.  Unlike other anti-CD20s, ublituximab can be delivered in shorter infusions, providing a convenience benefit for patients.