DMT03
Reduced Disease Progression with Ublituximab Vs Teriflunomide in the Phase 3 Ultimate I and II Studies in Relapsing Multiple Sclerosis

Thursday, June 2, 2022: 3:10 PM
Woodrow Wilson D (Gaylord National Resort & Convention Center)
Enrique Alvarez, MD, PhD , University of Colorado, Aurora, CO
Lawrence Steinman, MD , Beckman Center for Molecular Medicine, Stanford University Medical Center, Stanford, CA
Edward J Fox, MD, PhD , Central Texas Neurology Consultants, Multiple Sclerosis Clinic of Central Texas, Round Rock, TX
Hans-Peter Hartung, MD , Heinrich Heine University, Dusseldorf, Germany, Brain and Mind Centre, University of Sydney, Sydney, Australia, Department of Neurology, Medical University of Vienna, Vienna, Austria, Department of Neurology, Palacky University, Olomouc, Czech Republic
Peiqing Qian, MD , Swedish Medical Center, Seattle, WA
Sibyl Wray, MD , Hope Neurology MS center, Knoxville, TN
Derrick Robertson, MD , University of South Florida, Tampa, FL
DeRen Huang, MD, PhD , Center for Multiple Sclerosis, Mount Carmel Health System, Westerville, OH
Krysztof Selmaj, MD, PhD , Center of Neurology, Lodz, Poland, Department of Neurology, University of Warmia & Mazury, Olsztyn, Poland
Daniel Wynn, MD , Consultants in Neurology MS Center, Northbrook, IL
Lily Lee, PhD , TG Therapeutics, New York, NY
Bruce A Cree, MD, PhD, MAS , UCSF Weill Institute for Neurosciences, Department of Neurology, University of California San Francisco, San Francisco, CA



Background: Ublituximab is a novel monoclonal antibody targeting a unique epitope on the CD20 antigen. It is glycoengineered for enhanced antibody-dependent cellular cytotoxicity and is administered in 1-hour maintenance infusions after the first infusion. In the ULTIMATE I and II studies in patients with relapsing multiple sclerosis (RMS), ublituximab met its primary endpoint of significantly reduced annualized relapse rate vs teriflunomide. Ublituximab also provided significant improvements in the number of gadolinium-enhancing T1 lesions, number of new/enlarging T2 lesions, and proportion of patients with no evidence of disease activity. The secondary endpoint of 12-week confirmed disability progression was not met per the prespecified statistical plan for the individual studies.

Objectives: To further characterize disability progression with ublituximab.

Methods: ULTIMATE I (N=549) and II (N=545) evaluated ublituximab 450 mg intravenous 1-hour infusion every 24 weeks (following Day 1 infusion of 150 mg and Day 15 infusion of 450 mg) or teriflunomide 14 mg oral once daily for 96 weeks in patients with RMS. Pooled post hoc analyses of 12-week confirmed and unconfirmed disability progression, as well as Expanded Disability Status Scale (EDSS) score area under the curve (AUC), were conducted.

Results: In patients with confirmed 12-week disability progression, the mean change from baseline in EDSS score was statistically significant for ublituximab vs teriflunomide at Week 84 (0.8 vs 1.2, respectively; P=0.047) and Week 96 (0.9 vs 1.4, respectively; P=0.022). The proportion of patients with disability progression (12-week confirmed or unconfirmed) during the 96-week study period was 15.3% and 25.3% in the ublituximab (n=83) and teriflunomide (n=138) groups, respectively. The time to confirmed or unconfirmed disability progression was significant in favor of ublituximab (stratified hazard ratio [95% confidence interval], 0.586 [0.443-0.774]; P=0.0001). The mean AUC change in EDSS score during the study was -0.176 for ublituximab and -0.052 for teriflunomide, a difference of -0.124 (P=0.0079).

Conclusions: Pooled post hoc analyses demonstrated a significant improvement in multiple measures of disability progression with ublituximab vs teriflunomide in the ULTIMATE I and II studies.

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