Siponimod delays time to wheelchair

Secondary progressive MS is associated with insidious worsening of walking disability, which eventually results in increased wheelchair dependence [1]. Recently, it was shown that siponimod is efficacious in slowing down disability progression and cognitive decline in a typical secondary progressive MS population [2].

EXPAND was the largest phase 3 trial conducted in a typical secondary progressive MS population (n=1,651), with >50% of patients needing a walking aid (EDSS ≥6.0) at baseline. An open-label extension for up to 10 years is ongoing [2]. A significant delay in the risk of 3- and 6-month confirmed disability progression (CDP) was observed in siponimod-treated patients compared to the placebo group.

In the current study, the effect of siponimod in delaying time to wheelchair dependence was evaluated. In the survival analysis, a significantly lower proportion of siponimod-treated patients with baseline EDSS of 6.5 (19.8% vs 26.1%) progressed to EDSS ≥7 compared to placebo (HR 0.64; P=0.0483). Under the assumption of the model, i.e. a stable effect over time, siponimod extended the median time to EDSS ≥7 by 4.3 years in the overall population compared to placebo (12.0 years vs 16.3 years) [3].

Time to wheelchair is a highly clinically relevant endpoint. Prof. Patrick Vermersch (Lille University, France) thinks that results from this analysis translate to potential long-term benefits beyond the core part of the EXPAND trial. “Of course, extrapolation beyond the study duration is a limitation”, he added.

1. Bencsik K, et al. Eur Neurol. 2001;46:206-9.
2. Kappos L, et al. Lancet. 2018;391:1263-1273.
3. Vermersch P, et al. ECTRIMS 2019, abstract 158.

Posted on 8 November, 201925 March, 2024