Positive results from ublituximab versus teriflunomide

Results from the identical ULTIMATE I and II phase 3 trials showed that the novel anti-CD20 monoclonal antibody ublituximab significantly reduced the annualised relapse rate (ARR) and MRI abnormalities compared with teriflunomide in patients with relapsing MS.

Ublituximab targets a unique epitope on the CD20 antigen and is glycoengineered for enhanced B-cell depletion through antibody-dependent cellular cytotoxicity (ADCC). The increased ADCC may offer benefit over available anti-CD20 agents in terms of lower doses and shorter infusion times.

In the global, active-controlled, phase 3 studies ULTIMATE I (NCT03277261) and ULTIMATE II (NCT03277248), ublituximab was compared with teriflunomide in relapsing MS patients. Overall, 1,094 patients (ULTIMATE I, n=549; ULTIMATE II, n=545) participated in 10 countries. They were randomised 1:1 for 96 weeks to 450 mg ublituximab via 1-hour IV-infusions every 24 weeks (following 150 mg on day 1) or to 14 mg oral teriflunomide once daily. Participants were between 18 and 55 years of age (mean 36 years), with scores on the Expanded Disability Status Scale (EDSS) between 0 and 5.5. The primary endpoint was ARR, key secondary endpoints included MRI, no evidence of disease activity (NEDA), confirmed disability progression (CDI), and safety/tolerability.

Both studies met their primary endpoint of significantly reduced ARR (P<0.005 in each study). In ULTIMATE I, ARR was 0.076 in the ublituximab group and 0.188 in the teriflunomide group (adjusted ARR ratio 0.406; 95% CI 0.268–0.615). In ULTIMATE II, the ARR was 0.091 and 0.178, respectively (ARR ratio 0.509; 95% CI 0.330–0.784). The total number of relevant MRI abnormalities was reduced by 97% and by 96% with ublituximab versus teriflunomide in ULTIMATE I and II, respectively. In ULTIMATE I and II, 44.6% and 43.0% of ublituximab-treated patients achieved NEDA, respectively, representing a 198% and 277% improvement over teriflunomide (P<0.0001 for both studies). Ublituximab also significantly improved disability: compared with teriflunomide, the chance of CDI was 116% (P=0.003) in the first trial, and 103% (P=0.0026) in the second trial.

Ublituximab was generally well tolerated, with no significant differences in the percentage of adverse events (AEs) in the 2 study groups. In the ublituximab group, 9.5% reported a serious AE, compared with 6.2% in the teriflunomide group. Infection was more frequent in the ublituximab group: 4.0% versus 2.6%.

1. Steinman L, et al. Ublituximab versus teriflunomide in relapsing multiple sclerosis (RMS): Results of the Phase 3 ULTIMATE I and II trials. OPR-086, EAN 2021 Virtual Congress, 19–22 June.

 

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Posted on 18 August, 202125 March, 2024