Efficacy and safety of ublituximab versus teriflunomide in relapsing multiple sclerosis: Results of the Phase 3 ULTIMATE I and II trials
Lawrence Steinman1, Edward Fox2, Hans-Peter Hartung3, Enrique Alvarez4, Peiqing Qian5, Sibyl Wray6, Derrick Robertson7, Deren Huang8, Krzysztof Selmaj9, Daniel Wynn10, Michael Weiss11, Jenna Bosco11, Sean Power11, Koby Mok11, Bruce Cree12
1Stanford University, 2Central Texas Neurology Consultants, PA, 3Heinrich Heine University Duesseldorf, 4University of Colorado, 5Swedish Medical Center, 6Hope Neurology MS Center, 7University of South Florida, 8MDH Research, 9Medical Academy of Lodz, 10Consultants in Neurology, Ltd., 11TGTX, 12UCSF, Multiple Sclerosis Center
Objective:
 ULTIMATE-I (NCT03277261) and ULTIMATE-II (NCT03277248), are identical Phase 3, randomized, multi-center, double-blinded, active-controlled studies evaluating the efficacy and safety of UTX in patients (pts) with relapsing multiple sclerosis (RMS).  
Background:

Ublituximab (UTX), a novel monoclonal antibody, targets a unique epitope on the CD20 antigen and is glyco-engineered for enhanced B-cell  cytolysis through antibody-dependent cellular cytotoxicity (ADCC). The potent ADCC activity is thought to enhance B-cell depletion, and may allow lower doses and shorter infusions times versus other presently available anti-CD20s mAbs.

Design/Methods:

Pts were randomized (1:1) to receive either 450mg UTX via one-hour IV-infusion every 24 wks (following day 1 150mg UTX infusion) or 14mg oral teriflunomide QD, throughout a 96-week treatment period. Eligible pts had a diagnosis of RMS (McDonald Criteria 2010), Expanded Disability Status Scale (EDSS) score of 0-5.5, and age of 18-55 years. Pts were required to have >2 documented relapses within the 2 years prior, 1 relapse in the year prior, and/or >1 Gd-enhancing lesions in the year prior to screening. The primary endpoint is annualized relapse rate (ARR). Key secondary endpoints include MRI-related outcomes, no evidence of disease activity (NEDA), and 3-month confirmed disability progression. Safety and tolerability are also assessed.

Results:
Overall, 1094 pts were randomized in 10 countries (ULTIMATE I, N=549; ULTIMATE II, N=545). Baseline demographic and disease characteristics previously reported included mean age ~37 and ~35 years, mean MS duration since diagnosis of 4.7 and 5 years, and mean EDSS 2.9 and 2.9, respectively in ULTIMATE-I&II. Efficacy and safety results, including primary and key secondary endpoints, will be available at the meeting.
Conclusions:
ULTIMATE I&II will elucidate the therapeutic potential of a one-hour 450mg ublituximab infusion every six months for pts with RMS.