Siponimod vs placebo in active secondary progressive multiple sclerosis: a post hoc analysis from the phase 3 EXPAND study
Ralf Gold, Daniela Piani-Meier, Ludwig Kappos, Amit Bar‐Or, Patrick Vermersch, Gavin Giovannoni, Robert J. Fox, Douglas L. Arnold, Ralph H. B. Benedict, Iris‐Katharina Penner, Nicolas Rouyrre, Ajay Kilaru, Göril Karlsson, Shannon Ritter, Frank Dahlke, Thomas Hach, Bruce Cree
Abstract
Abstract Background Siponimod is a sphingosine 1-phosphate receptor modulator approved for active secondary progressive multiple sclerosis (aSPMS) in most countries; however, phase 3 EXPAND study data are from an SPMS population with/without disease activity. A need exists to characterize efficacy/safety of siponimod in aSPMS. Methods Post hoc analysis of participants with aSPMS (≥ 1 relapse in 2 years before study and/or ≥ 1 T1 gadolinium-enhancing [Gd +] magnetic resonance imaging [MRI] lesions at baseline) receiving oral siponimod (2 mg/day) or placebo for up to 3 years in EXPAND. Endpoints: 3-month/6-month confirmed disability progression (3mCDP/6mCDP); 3-month confirmed ≥ 20% worsening in Timed 25-Foot Walk (T25FW); 6-month confirmed improvement/worsening in Symbol Digit Modalities Test (SDMT) scores (≥ 4-point change); T2 lesion volume (T2LV) change from baseline; number of T1 Gd + lesions baseline–month 24; number of new/enlarging (N/E) T2 lesions over all visits. Results Data from 779 participants with aSPMS were analysed. Siponimod reduced risk of 3mCDP/6mCDP vs placebo (by 31%/37%, respectively; p < 0.01); there was no significant effect on T25FW. Siponimod increased likelihood of 6-month confirmed SDMT improvement vs placebo (by 62%; p = 0.007) and reduced risk of 6-month confirmed SDMT worsening (by 27%; p = 0.060). Siponimod was associated with less increase in T2LV (1316.3 vs 13.3 mm 3 ; p < 0.0001), and fewer T1 Gd + and N/E T2 lesions than placebo (85% and 80% reductions, respectively; p < 0.0001). Conclusions In aSPMS, siponimod reduced risk of disability progression and was associated with benefits on cognition and MRI outcomes vs placebo. Trial registration ClinicalTrials.gov number : NCT01665144.