Late-breaking: Ofatumumab versus teriflunomide in relapsing MS

Ofatumumab is the first fully human anti-CD20 mAb, which is under development for the treatment of MS. Ofatumumab binds to CD20, resulting in B-cell depletion and reduced B- and T-cell interactions, which may reduce inflammation in the central nervous system. Anti-CD20 therapy may preserve pre-existing humoral immunity and B-cell reconstitution [1].

Two phase 3 trials, identical in design and conducted in parallel, ASCLEPIOS I and II (n=1,881 totally), evaluated the effect of ofatumumab in patients with relapsing MS. Ofatumumab demonstrated significant reduction of adjusted annualised relapse rate (ARR):

• ASCLEPIOS I: 0.22 in teriflunomide group vs 0.11 in ofatumumab group (relative reduction of 50.5%; P<0.001); and
• ASCLEPIOS II: 0.25 in teriflunomide group vs 0.10 in ofatumumab group (relative reduction of 58.5%; P<0.001, see Figure) [2].

Figure. Ofatumumab demonstrated significant reduction in ARR (primary endpoint in full analysis set) [2]



Furthermore, ofatumumab showed a significant reduction in 3- and 6-month confirmed disability worsening (CDW) and a favourable, but non-significant trend to achieve 6-month confirmed disability improvement (CDI):

• 3-month CDW: 15.0% in teriflunomide group vs 10.9% in ofatumumab group (relative reduction of 34.4%; P=0.002; HR 0.656);
• 6-month CDW: 12.0% in teriflunomide group vs 8.1% in ofatumumab group (relative reduction of 32.5%; P=0.012; HR 0.675); and
• 6-month CDI: 8.1% in teriflunomide group vs 11.0% in ofatumumab group (relative increase of 35.2%; P=0.094; HR 1.352) [2].

The ASCLEPIOS I and II trials demonstrated, in a broad population of patients with active, somewhat advanced relapsing MS, that ofatumumab has superior efficacy compared with teriflunomide in lowering relapse rates and MRI activity. Treatment with ofatumumab leads to substantial and significant reductions in 3- and 6-month CDW, and to lower levels of neurofilament light chain (NfL) already at month 3 and at all subsequent visits. Ofatumumab also had a favourable safety profile with no unexpected safety signals. There was no imbalance in the rates of infections or malignancies (low on both arms of the trial).

1. Dalakas MC. Nat Clin Pract Neurol. 2008;4:557-67.
2. Hauser SL, et al. ECTRIMS 2019, abstract 336.

Posted on 8 November 201925 March 2024