From the Journals

Siponimod trial ‘first’ to show delayed disability in secondary progressive MS



Phase 3 data with siponimod, Novartis’ investigational treatment for multiple sclerosis, show a 21% reduction in the time to disease progression versus placebo in patients with the secondary progressive subtype of the disease.

A significantly lower percentage of patients with secondary progressive multiple sclerosis (SPMS) treated with siponimod met the primary endpoint of confirmed disease progression (CDP) at 3 months, compared with those who received placebo in the EXPAND trial (26% vs. 32% of patients; hazard ratio [HR], 0.79; 95% confidence interval [CI], 0.65–0.95; P = .013).

Multiple sclerosis is written on the screen of a tablet. HUNG KUO CHUN/Thinkstock
“The siponimod EXPAND study is, to our knowledge, the first large trial of any disease-modifying therapy to show superiority over placebo in terms of disability progression in a representative population of patients with SPMS,” lead author Ludwig Kappos of University Hospital, University of Basel (Switzerland), and his coinvestigators reported online March 22 in The Lancet. The study population involved “a large proportion of patients who had reached the non-relapsing stage of SPMS and had a high level of established disability,” they observed.

No significant difference between siponimod and placebo was seen in one of the two main secondary outcomes of the study – the time to 3-month confirmed worsening of the timed 25-foot walk test (T25FW). This result led Luanne Metz, MD, and Wei-Qiao Liu, MD, both of the department of clinical neurosciences and the Hotchkiss Brain Institute at the University of Calgary (Alta.), to take a cautionary view of the findings in an editorial about the trial’s results.

“Although siponimod seems to reduce the time to confirmed disability in SPMS, the treatment effect was small,” Dr. Metz and Dr. Liu argued.

“In our opinion, the reduction in the proportion of participants reaching the primary endpoint of only 6% and the absence of a significant difference for the key secondary clinical outcome [T25FW] are disappointing results and do not suggest that siponimod is an effective treatment for SPMS,” the two wrote.

“Confidence in the treatment benefit of siponimod in progressive MS will, in our opinion, require confirmation in a second trial. Trials of other novel treatments that target noninflammatory mechanisms are still needed,” they said.


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