Ublituximab versus teriflunomide in relapsing MS patients

In both the phase 3 ULTIMATE I and ULTIMATE II trial, ublituximab treatment demonstrated a statistically significant reduction in annualised relapse rate (ARR) and cumulative probability of first relapse compared with teriflunomide over 96 weeks in patients with relapsing multiple sclerosis (RMS).

Ublituximab is an investigational monoclonal antibody that targets a unique epitope on the CD20 antigen [1]. Binding to B cells, ublituximab triggers a series of immunological reactions, including antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). It is glyco-engineered to enhance ADCC [2].

ULTIMATE I (NCT03277261) (n=549) and ULTIMATE II (NCT03277248) (n=545) are 2 independent phase 3, randomised, double-blind, active-controlled, global studies that evaluate the efficacy and safety/tolerability of ublituximab (450 mg intravenous infusion every 24 weeks, following a Day 1 infusion of 150 mg) versus teriflunomide (14 mg orally once daily) for 96 weeks. Participants were patients with RMS from 10 countries and most had relapsing-remitting MS, while about 2% had active secondary-progressive MS. In both studies, ublituximab previously showed significant relative improvements in absolute risk reduction and radiographic disease activity [3]. Pre-specified analyses looked at the proportion of participants who were relapse-free and the time to first relapse. Prof. Lawrence Steinman (Stanford University, CA, USA) presented the results [4].

In the ULTIMATE I study, 86.7% versus 75.2% of participants were free of relapse with ublituximab and teriflunomide, respectively, after 96 weeks. In the ULTIMATE II study, these percentages were 87.5% and 73.5%, respectively. The estimated proportion of participants who remained relapse-free was higher with ublituximab than with teriflunomide in both studies.

The cumulative probability of first confirmed relapse was significantly lower with ublituximab in both studies than with teriflunomide. In ULTIMATE I the HR was 0.50 (95% CI 0.33–0.75; P=0.0007); in ULTIMATE II, the HR was 0.43 (95% CI 0.28–0.65; P<0.0001; see Figure).

Figure: Time to first confirmed relapse in Ultimate I and Ultimate II [3]



 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

1. Babiker HM, et al. Expert Opin Investig Drugs. 2018;27(4):407‒412.


2. Butler LA, et al. Blood Reviews. 2017;31(5):318‒327.


3. Steinman L, et al. Abstract A-21–0076, EAN 2021, 19–22 June.


4. Steinman L, et al. Relapse Rate and Time to First Relapse Were Improved With Ublituximab vs Teriflunomide in the Phase 3 ULTIMATE I and ULTIMATE II Studies in Patients With Relapsing Multiple Sclerosis (RMS). Clinical Trials plenary session, AAN 2022, 02–07 April, Seattle, USA.

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Posted on 2 June, 2022