Ublituximab Efficacy in Treatment-Naive Participants With Relapsing Multiple Sclerosis in the Phase 3 ULTIMATE I and II Studies
Lawrence Steinman1, Edward Fox2, Hans-Peter Hartung3, Enrique Alvarez4, Peiqing Qian5, Sibyl Wray6, Derrick Robertson7, Deren Huang8, Krzysztof Selmaj9, Daniel Wynn10, Jenna Bosco11, Koby Mok11, Christopher A Garner11, Bruce Cree12
1Stanford Medicine, 2Central Texas Neurology Consultants, 3Heinrich Heine University Düsseldorf, 4University of Colorado, 5Swedish Medical Center, 6Hope Neurology, 7University of South Florida, 8Mount Carmel Neurology, 9University of Warmia and Mazury, 10Consultants in Neurology, Ltd., 11TG Therapeutics, 12UCSF, Multiple Sclerosis Center
Objective:
To evaluate efficacy with ublituximab in treatment-naive participants with relapsing multiple sclerosis enrolled in ULTIMATE I and II.
Background:
Ublituximab is a novel monoclonal antibody targeting a unique epitope of CD20. Ublituximab is glycoengineered for enhanced antibody-dependent cellular cytotoxicity and is administered in 1-hour infusions after the first infusion. In ULTIMATE I and II, ublituximab significantly improved annualized relapse rate (ARR) 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 who had not received approved disease-modifying therapy (DMT) within 5 years prior to study enrollment. The pooled treatment-naive population included 345 ublituximab and 377 teriflunomide participants evaluable for clinical outcomes, and 340 and 372, respectively, evaluable for radiographic outcomes.
Results:
In the treatment-naive population, the adjusted ARR was 0.081 versus 0.188 for ublituximab versus teriflunomide (P<0.0001), and by Kaplan-Meier estimate, 11.2% versus 5.5% achieved 12-week confirmed disability improvement at Week 96; hazard ratio (95% CI), 2.031 (1.174-3.513; P=0.0095). For ublituximab versus teriflunomide, the total number (least squares means) of gadolinium-enhancing T1 lesions per scan was 0.031 versus 0.791; for new/enlarging T2 lesions, 0.390 versus 4.144 (both P<0.0001). Change from baseline in Multiple Sclerosis Functional Composite score was 0.53 versus 0.28 for ublituximab versus teriflunomide (P=0.0047). No evidence of disease activity rates (Weeks 24-96, re-baselined) with ublituximab (n=324) versus teriflunomide (n=350) were 82.7% versus 23.1% (P<0.0001). Occurrence of 12-week confirmed disease progression was low in both treatment groups.
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 who had not received prior DMT.