Ublituximab Significantly Reduces Radiological Disease Activity at 12 Weeks: Post-hoc analysis of Participants with Highly Active Disease in the ULTIMATE I & II Phase 3 Studies
Derrick Robertson1, Hans-Peter Hartung2, Douglas Arnold3, Lily Lee4, Anne Gocke4, Koby Mok4, Enrique Alvarez5
1University of South Florida, 2Heinrich Heine University Medical Faculty, 3Montreal Neurological Institute, McGill Univ, 4TG Therapeutics, 5University of Colorado
Objective:

To evaluate the impact of ublituximab on radiologic outcomes and NEDA at 12 weeks in participants with highly active disease at baseline in the phase 3 ULTIMATE I and II studies.

Background:

Ublituximab is a novel monoclonal antibody targeting CD20 and is glycoengineered for enhanced antibody-dependent cellular cytolysis. In the ULTIMATE I and II studies, ublituximab significantly reduced annualized relapse rate and radiologic disease activity vs teriflunomide. Therapies that impact disease activity early in people with highly active disease can play a crucial role in limiting neurologic damage.

Design/Methods:
The ULTIMATE I (N=549) and II (N=545) studies evaluated ublituximab 450 mg IV infusion every 24 weeks vs teriflunomide 14 mg orally once daily for 96 weeks.  Post hoc analyses at week 12 were performed to evaluate the number of Gd+ T1 lesion counts, (n/e) T2 lesion counts and NEDA in a subgroup of people with highly active disease (≥ 2 relapses in prior year and ≥ 1 Gd+ lesion at baseline).
Results:
Ublituximab treatment resulted in an 83% reduction in Gd+ T1 lesions compared with teriflunomide at week 12 (least squares (LS) mean (95% CI) = 0.114 vs 0.683 for ublituximab vs teriflunomide respectively (P<0.0001)). 88% of participants were free from Gd+ lesions in the ublituximab treated group (P<0.0001). The number of n/e T2 lesions at 12 weeks was also significantly reduced in this population (58% reduction; LS mean = 1.754 vs 4.127 for ublituximab and teriflunomide, respectively). A significantly higher proportion of ublituximab participants achieved NEDA compared to teriflunomide at week 12 (30% vs. 10%; P=0.0012).
Conclusions:
Ublituximab significantly reduced key MRI measures of disease activity at 12 weeks in a subgroup of participants with highly active disease at baseline, with 30% of people achieving NEDA. These results could be beneficial in managing disease and limiting future accumulation of disability in this population.
10.1212/WNL.0000000000206192