The sphingosine-1-phosphate receptor modulator siponimod reduces the risk of disability progression compared with placebo in people with secondary progressive multiple sclerosis (SPMS), according to the results of a phase III trial
The researchers say the findings represent the first time that a treatment has been shown to slow disability progression in a population with this advanced form of the disease.
“So far, no drug has consistently reduced disability progression in people with secondary progressive multiple sclerosis,” said lead author Ludwig Kappos from the University of Basel, Switzerland. “These patients often have a high level of disability, and preventing further progression is important for their quality of life.”
The study, reported in The Lancet, involved 1,099 patients randomly assigned to siponimod and 546 to placebo, who were followed for up to three years (median: 21 months). The researchers studied the time to three-month confirmed disability progression (CDP), an increase in the Expanded Disability Scale Score (EDSS) sustained over three months.
The team found that 288 (26%) patients assigned to siponimod had a three-month CDP compared with 173 (32%) of those assigned to placebo, equating to a 21% relative risk reduction. There was also a 26% reduction in the risk of six-month CDP.
MRI results also showed that loss of brain volume progressed at a significantly lower rate in the siponimod group compared with placebo over 12 and 24 months.
The researchers said the safety profile is similar to other sphingosine-1-phosphate receptor modulators. Overall, 89% of those assigned to siponimod and 82% assigned to placebo experienced adverse events, while serious adverse events occurred for 18% and 15% of participants, respectively.
Patients with MS usually present with the relapsing-remitting form of the illness and many will go on to develop secondary progressive MS within 15–20 years. The sphingosine-1-phosphate receptor modulator fingolimod was approved by the European Medicines Agency in 2011 for relapsing MS, which includes relapsing SPMS. However, no immunomodulatory therapy has been shown to be effective in the subgroup of patients with SPMS in clinical trials. In this trial, 64% of the participants had not relapsed within the previous two years, indicating more severe disease, and more than half required walking aids.
The researchers said their findings were likely to be clinically significant for patients with this level of established disability as a 0.5 difference in EDSS score can equate to requiring two walking aids instead of one, or becoming unable to walk more than a few steps without support.
However, Kappos concluded: “Although the effects of the drug on disability progression after three and six months are impressive, our study does not yet look at the long-term effects of siponimod, which we are investigating in the long-term follow-up of the study patients.”
 Kappos L, Bar-Or A, Cree B et al. Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a double-blind, randomised, phase 3 study. The Lancet 2018;391(10127):1263–1273. doi: 10.1016/S0140-6736(18)30475-6