Disease Outcomes With Ublituximab in Participants With Highly Active Disease: Subpopulation Analyses of the Phase 3 ULTIMATE I and II Studies in Participants With Relapsing Multiple Sclerosis
Enrique Alvarez1, Lawrence Steinman2, Hans-Peter Hartung3, Edward Fox4, Peiqing Qian5, Sibyl Wray6, Derrick Robertson7, Koby Mok8, Christopher A Garner8, Bruce Cree9
1University of Colorado, 2Stanford Medicine, 3Heinrich Heine University Medical Faculty Departme, 4Central Texas Neurology Consultants, 5Swedish Medical Center, 6Hope Neurology, 7University of South Florida, 8TG Therapeutics, 9UCSF, Multiple Sclerosis Center
Objective:
To evaluate efficacy with ublituximab in participants enrolled in ULTIMATE I and II with highly active disease at baseline.
Background:
Ublituximab is a novel anti-CD20 monoclonal antibody glycoengineered for enhanced antibody-dependent cellular cytotoxicity and is administered in 1-hour infusions after the first infusion. In the Phase 3 ULTIMATE I and II studies in participants with relapsing multiple sclerosis, ublituximab demonstrated significantly improved annualized relapse rate (ARR) and significant reductions in gadolinium-enhancing (Gd+) T1 lesions and new/enlarging T2 lesions versus teriflunomide.
Design/Methods:
The Phase 3 ULTIMATE I (N=549) and II (N=545) studies evaluated ublituximab 450 mg intravenous infusion every 24 weeks or teriflunomide 14 mg oral once daily for 96 weeks. Pooled post hoc subpopulation analyses evaluated efficacy measures at Week 96 in participants with highly active disease, defined as ≥2 relapses in the year prior and ≥1 Gd+ T1 lesion at baseline.
Results:
In the highly active population, the unadjusted ARR was 0.145 and 0.496 for ublituximab (n=88) and teriflunomide (n=80) groups, respectively (P<0.0001). The total number (least squares means) of Gd+ T1 lesions and new/enlarging T2 lesions per scan was 0.038 versus 0.875 and 0.568 versus 6.367 for ublituximab versus teriflunomide (both P<0.0001). No evidence of disease activity rates (Weeks 24-96, re-baselined) with ublituximab versus teriflunomide were 77.9% versus 16.4% (P<0.0001). Percent brain volume change (Weeks 24-96, re-baselined) was -0.614 and -0.664 for the ublituximab and teriflunomide groups, respectively. The occurrence of 12-week confirmed disability progression was low in both treatment groups (8.0% ublituximab; 5.0% teriflunomide).
Conclusions:
In pooled post hoc analyses of ULTIMATE I and II, ublituximab was associated with significant treatment benefit across multiple efficacy measures at Week 96 versus teriflunomide in participants with highly active disease at baseline.