Ublituximab versus teriflunomide in relapsing MS

In the phase 2 ULTIMATE I and II trials, ublituximab significantly reduced annualised relapse rate (ARR) and MRI parameters compared with teriflunomide in relapsing multiple sclerosis (MS) patients. A very low rate of disability progression was observed with ublituximab, with >94% of patients showing no 12-week confirmed disease progression.

ULTIMATE I (NCT03277261) and ULTIMATE II (NCT03277248) are identical phase 3, randomised, multicentre, double-blinded, active-controlled studies. The studies' objective was to evaluate the efficacy and safety of ublituximab compared with teriflunomide in relapsing MS patients [1]. In both trials, participants were randomised 1:1 to intravenous ublituximab every 24 weeks or daily oral teriflunomide for 96 weeks. The primary endpoint was ARR at week 96. Key secondary endpoints included MRI-related outcomes, no evidence of disease activity (NEDA), and 3-month confirmed disability progression.

In both studies, ublituximab was associated with a relative reduction in ARR of 60% (P<0.0001) and 49% (P=0.0022), respectively (see Figure). There was a relative reduction in the total number of Gd-enhancing T1 lesions with ublituximab of 97% and 96%, respectively, relative to teriflunomide (P<0.0001). The relative reduction in the total number of new or enlarging T2 lesions was 92% and 90%, respectively, relative to teriflunomide (P<0.0001). In a prespecified pooled tertiary analysis, there was a 100% improvement in the proportion of patients who reached 12-week confirmed disability improvement (CDI) with ublituximab versus teriflunomide (12% vs 6%; HR 2.158; 95% CI 1.406–3.3133). There was an 88% improvement in 24-week CDI (9.6% vs 5.1%; HR 2.031; 95% CI 1.269­–3.248). In ULTIMATE I, 44.6% of patients in the ublituximab group achieved NEDA, which is a relative increase by 198% over teriflunomide (P<0.0001). In ULTIMATE II, 43% achieved NEDA, an increase of 277% over teriflunomide (P<0.0001). Ublituximab had a favourable safety and tolerability profile with no unexpected safety signals.

Figure: ARR at 96 weeks in ULTIMATE I and II trials [1]



ARR, annualised relapse rate.

1. Steinman L, et al. Efficacy and safety of ublituximab versus teriflunomide in relapsing multiple sclerosis: Results of the Phase 3 ULTIMATE I and II trials. P15.074, AAN 2021 Virtual Congress, 17-22 April.

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Posted on 16 June, 2021