- Steinman L, et al. Phase 3 results of the ULTIMATE I & II global studies: ublituximab versus teriflunomide in relapsing multiple sclerosis. OP117, ECTRIMS 2021 Virtual Congress, 13—15 October
Ublituximab is a novel anti-CD20 monoclonal antibody, currently under investigation for the treatment of MS. The new agent is glycoengineered to allow for lower doses and only 1-hour infusion time after the initial infusion. This study presented the 96-week results of the randomised, multi-centre, double-blind, ULTIMATE I (NCT03277261) and ULTIMATE II (NCT03277248) phase 3 trials.
In both trials subjects with confirmed relapsing MS (n=549, n=545) were randomised 1:1 to receive ublituximab or 14 mg teriflunomide (oral, once daily). Patients in the ublituximab arm received 150 mg intravenous infusion at day 1, followed by 450 mg 1-hour IV infusion at day 15, and then every 24 weeks. The primary endpoint was the annualised relapse rate at week 96. Prof. Lawrence Steinman (Stanford University, CA, USA) presented the findings.
Ublituximab significantly reduced the annualised relapse rate (ARR) in the ULTIMATE I (59.4% reduction) and II (49.1% reduction) trials compared with teriflunomide. The relative reductions of contrast enhancing T1 lesions for patients in the ublituximab arms were 96.7% and 96.5%, respectively, as compared with teriflunomide. The relative reductions of new or enlarging T2 lesions displayed similar results. In both trials, the proportion of patients who showed No Evidence of Disease Activity (NEDA) were higher in ublituximab receivers (44.6%; 43.0%) than in teriflunomide receivers (15.0%; 11.4%).
Multiple Sclerosis Functional Composite (MSFC) scores displayed patients benefitted from ublituximab (0.469; 0.521) over teriflunomide (0.266; 0.275). A favourable safety and tolerability profile was observed for ublituximab. Any adverse events (AEs) were reported in approximately 88% of the patients, regardless of treatment arm. Infusion-related reactions, headache, and nasopharyngitis were the most reported AEs in the ublituximab arm. Serious AEs were observed in 9.5% of the patients treated with ublituximab, being mostly infections and infestations.