Superior effect of ponesimod versus teriflunomide on clinical disease activity and MRI-based outcomes

In the phase 3 OPTIMUM study, ponesimod showed benefit compared with teriflunomide on all MRI outcomes, including brain volume loss. A significantly higher proportion of patients achieved NEDA-3 and NEDA-4 status. These findings support the previously observed effect of ponesimod on clinical endpoints in patients with relapsing MS.

Ponesimod is an orally active, selective sphingosine-1-phosphate receptor modulator that causes dose-dependent sequestration of lymphocytes in lymphoid organs, thereby reducing the blood count. In the phase 3 OPTIMUM study (NCT02425644), ponesimod demonstrated superior efficacy compared to teriflunomide in reducing annualised relapse rate (ARR) in patients with relapsing-remitting MS. The current analysis of the OPTIMUM study evaluated prespecified MRI-based endpoints and ‘no evidence of disease activity’ (NEDA) status [1].

A total of 985 (86.9%) randomised patients completed the study. MRI findings for ponesimod versus teriflunomide, respectively, were:

• LS mean percent change in brain volume: −0.91% versus −1.25% (P<0.0001);
• LS mean difference for change in total T2-lesion load: −399.2 mm³ (P=0.002);
• mean number of new and enlarging T2-lesions per year: 1.40 versus 3.16 (rate ratio 0.44, P<0.0001; OR for absence of new/enlarging T2-lesions: 1.71, P=0.0001);
• mean number of new Gd+ T1-lesions per scan: 0.18 versus 0.43 (RR 0.42, P<0.0001; OR for absence of new Gd+ T1-lesions: 2.18, P<0.0001).

At week 108, 28.2% of ponesimod-treated patients and 18.3% of teriflunomide-treated patients achieved NEDA-3 (OR 1.70, P=0.0004) and 15.0% versus 8.5% achieved NEDA-4 (OR 1.85, P=0.0026), respectively. The most common reason for not achieving NEDA-3 or NEDA-4 status was presence of new and enlarging T2-lesions.

1. Kappos L, et al. Effect of oral ponesimod on clinical disease activity and MRI-based outcomes in patients with relapsing MS: Phase 3 OPTIMUM study. ECF 28^th Annual Meeting. Abstract 34.

Posted on 16 December 20204 September 2023