Relapse Rate and Time to First Relapse Were Improved With Ublituximab vs Teriflunomide in the Phase 3 ULTIMATE I and ULTIMATE II Studies in Patients With Relapsing Multiple Sclerosis (RMS)
Lawrence Steinman1, Edward Fox2, Hans-Peter Hartung3,4,5,6, Enrique Alvarez7, Peiqing Qian8, Sibyl Wray9, Derrick Robertson10, DeRen Huang11, Krzysztof Selmaj12,13, Daniel Wynn14, Michael S. Weiss15, Jenna A. Bosco15, Sean A. Power15, Koby Mok15, Lily Lee15, Bruce Cree16
1Stanford University, 2Central Texas Neurology Consultants, 3Heinrich Heine University, 4Brain and Mind Centre, University of Sydney, 5Department of Neurology, Medical University of Vienna, 6Department of Neurology, Palacky University, 7University of Colorado, 8Swedish Medical Center, 9Hope Neurology, 10University of South Florida, 11Center for Multiple Sclerosis, Mount Carmel Health System, 12University of Warmia and Mazury, 13Center of Neurology, 14Consultants in Neurology, 15TG Therapeutics, 16UCSF Weill Institute for Neurosciences, University of California San Francisco
Objective:
To characterize the effects of ublituximab on relapse rate and time to first relapse.
Background:
Ublituximab, a novel monoclonal antibody targeting a unique epitope on the CD20 antigen, is glycoengineered for enhanced antibody-dependent cellular cytotoxicity and is administered in 1-hour maintenance infusions. The Phase 3 ULTIMATE I and II studies showed significant improvements in annualized relapse rate and radiographic disease activity vs teriflunomide at 96 weeks.
Design/Methods:
In ULTIMATE I (N=549) and II (N=545), patients with RMS received ublituximab 450 mg intravenous infusion every 24 weeks (following Day 1 infusion of 150 mg) or teriflunomide 14 mg oral once daily for 96 weeks. These prespecified analyses evaluated the proportion of patients who were relapse-free and the time to first relapse. 
Results:
In ULTIMATE I, 86.7% vs 75.2% and in ULTIMATE II, 87.5% and 73.5% of patients were free of relapse with ublituximab vs teriflunomide, respectively, at 96 weeks. The Kaplan-Meier estimates for proportion of patients free of relapse for ublituximab vs teriflunomide in ULTIMATE I was 96.2% vs 90.8%, 92.4% vs 83.6%, and 86.0% vs 74.4% at 24, 48, and 96 weeks, respectively. For ULTIMATE II it was 92.6% vs 90.7%, 90.0% vs 82.2%, 87.4% vs 72.1% at 24, 48, and 96 weeks, respectively. The cumulative probability of first confirmed relapse was significantly reduced with ublituximab in both studies compared with teriflunomide (ULTIMATE I: hazard ratio [HR], 0.50; 95% confidence interval [CI], 0.33-0.75; P=0.0007; ULTIMATE II: HR, 0.43; 95% CI, 0.28-0.65; P<0.0001).
Conclusions:
In the Phase 3 ULTIMATE I and II trials, relapse rate and cumulative probability of relapse were significantly reduced with ublituximab vs teriflunomide.