Ublituximab Treatment Is Associated With a Significant Proportion of Patients Achieving No Evidence of Disease Activity (NEDA): Results From the Ultimate I and Ultimate II Phase 3 Studies of Ublituximab vs Teriflunomide in Relapsing Multiple Sclerosis (RMS)
Enrique Alvarez1, Lawrence Steinman2, Edward Fox3, Hans-Peter Hartung4,5,6,7, 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
1University of Colorado, 2Stanford University, 3Central Texas Neurology Consultants, 4Heinrich Heine University, 5Brain and Mind Centre, University of Sydney, 6Department of Neurology, Medical University of Vienna, 7Department of Neurology, Palacky University, 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 NEDA.
Background:
Ublituximab, a novel monoclonal antibody, targets a unique epitope of CD20 and is glycoengineered for enhanced antibody-dependent cellular cytotoxicity. Phase 3 ULTIMATE I and II studies showed significant improvements in relapse rate, number of gadolinium-enhancing (Gd+) T1 lesions, new/enlarging T2 lesions, and NEDA for ublituximab 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. Post hoc pooled analyses evaluated NEDA by treatment epoch and patient subtype: treatment-naive (Tx-naive), prior disease-modifying therapy (Tx-exp), and ≤3 years (Early-dz) and >3 years (Late-dz) following diagnosis. NEDA was defined as no confirmed relapses, no T1 Gd+ lesions, no new/enlarging T2 lesions, and no 12-week confirmed disability progression.
Results:

NEDA rates for ublituximab vs teriflunomide cohorts by treatment epoch (weeks) were 0-96: 44.6% vs 12.4% (3.6x improvement); 24-96 (re-baselined): 82.1% vs 22.5% (3.6x improvement); 0-24: 53.3% vs 29.2% (1.8x improvement); 0-48: 49.3% vs 20.1% (2.5x improvement); and 48-96 (re-baselined): 88.2% vs 30.4% (2.9x improvement) (P<0.0001 for all). NEDA at 24-96 weeks (re-baselined) was achieved in 82.7% and 23.1% (3.6x improvement) of Tx-naive, 81.1% and 21.1% (3.8x improvement) of Tx-exp, 82.4% and 18.6% (4.4x improvement) of Early-dz, and 81.9% and 26.5% (3.1x improvement) of Late-dz patients in ublituximab- vs teriflunomide-treated cohorts, respectively (P<0.0001 for all). Disease activity during Weeks 24-96 (entire population) was relapse (11.4% vs 22.9%), progression (4.9% vs 6.3%), Gd+ lesions (0.6% vs 40.9%), and/or new/enlarging T2 lesions (3.1% vs 71.6%) in ublituximab vs teriflunomide patients.

Conclusions:
ULTIMATE I and II post hoc pooled analyses demonstrated a consistent NEDA benefit for ublituximab-treated patients across treatment epochs and key patient subpopulations.