Siponimod Delays Time to Wheelchair Use in Secondary Progressive MS


After showing significant benefits in delayed disease progression in patients with secondary progressive MS, new data suggests siponimod can delay the time to wheelchair dependence by 4 years.

Dr Patrick Vermersch

Patrick Vermersch, MD, PhD, vice-dean, faculty of medicine, University of Lille

Patrick Vermersch, MD, PhD

A new analysis of the EXPAND study population has suggested that siponimod (Mayzent, Novartis) may have an additional long-term benefit for patients with secondary progressive multiple sclerosis (MS) beyond the study’s core findings. The oral selective sphingosine-1-phosphate receptor modulator significantly delayed time to wheelchair dependence.1

The data were presented by Patrick Vermersch, MD, PhD, vice-dean, faculty of medicine, University of Lille, at ECTRIMS 2019, September 11-13 in Stockholm, Sweden. “Siponimod has been shown to reduce disability progression, not only physically based on Expanded Disability Status Scale [EDSS], but also reduced cognitive decline in a typical secondary progressive MS population,” he said in his presentation.

In the survival analysis conducted by Vermersch and colleagues, only 19.8% of siponimod-treated patients with a baseline EDSS of 6.5 progressed to a score of ≥7, compared to 26.1% of placebo patients, equating to a risk reduction of 36% (hazard ratio [HR], 0.64; 95% CI, 0.41—1.0; P = .0483). In the multistate model, a similar reduction of 21% risk of transitioning from EDSS ≤5 to 5.5—6 was shown for the siponimod group (HR, 0.79; 95% CI, 0.63–1.00), and a 28% risk reduction (HR, 0.72; 95% CI, 0.48–1.06) of transitioning from EDSS 6.5 to sustained EDSS ≥7.

“Under assumptions of the model that the treatment effect is preserved, siponimod delayed the median time to wheelchair by 4.3 years in the overall population compared to placebo. Of course, extrapolation beyond the study period is a great limitation,” Vermersch said. The siponimod-treated group extended their time from 12.0 years to 16.3 years.

Vermersch noted during the discussion section of his presentation that the group did not control for disease activity according to MRI—relapses and new lesions—as the EXPAND core data demonstrated siponimod’s effect on MRI measures of disease activity. “We have not done this analysis yet, but we need to do it, indeed,” he concluded.

The survival analysis was performed on the subgroup of patients who were at high risk of reaching wheelchair during the EXPAND study period (siponimod, n = 293; placebo, n = 119). The multistate model was conducted with the full EXPAND cohort (siponimod, n = 1099; placebo, n = 546), using 3 disease states, stratified by EDSS scores of ≤5, 5.5—6, and 6.5.

The treatment, which was approved by the FDA for secondary progressive disease in March 2019, was given the OK based on data from the EXPAND trial, which was the largest phase 3 assessment of its kind, including 1651 patients with secondary progressive MS. It ultimately shows that 3-month confirmed disability progression was reduced by 21% (P = .013) with siponimod treatment.2

The EXPAND trial additionally showed a 33% reduction in confirmed disability progression compared to placebo in patients with relapse activity in the 24 months prior to screening (P = .0100). As well, data revealed that the risk of 6-month confirmed disability progression was reduced by 26% compared to placebo (P = .0058) and that the annualized relapse rate was reduced by 55% with siponimod.

At the time of its approval, EXPAND investigator Robert Fox, MD, neurologist, Mellen Center for MS Treatment, Cleveland Clinic, told NeurologyLive that the breadth of the data gives siponimod a large-scale body of evidence supporting its use. “This is a very large and compelling dataset from which to draw our understanding regarding the drug’s efficacy. It shows us that SPMS can be treated, particularly when there is evidence for active inflammation,” he said.

Vermersch and colleagues concluded that these data further support the clinical relevance of siponimod’s impact on delaying physical disability progression in patients with secondary progressive disease.

For more coverage of ECTRIMS 2019, click here.


1. Vermersch P, Gold R, Kappos L, et al. Siponimod delays the time to wheelchair in patients with SPMS: results from the EXPAND study. Presented at: ECTRIMS 2019. September 11-13, 2019; Stockholm, Sweden. Abstract 158.

2. Kappos L, Cree B, Fox R, et al. Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a double-blind, randomized, phase 3 study. Lancet. Published online March 22, 2018. doi: 10.1016/S0140-6736(18)30475-6.

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