Siponimod vs placebo in active secondary progressive multiple sclerosis: a post hoc analysis from the phase 3 EXPAND study.

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 mm3; 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.

• Authors: 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 A C Cree
• Journal: Journal of neurology (J Neurol) Vol. 269 Issue 9 Pg. 5093-5104 (Sep 2022) ISSN: 1432-1459 [Electronic] Germany
• PMID: 35639197 (Publication Type: Journal Article, Randomized Controlled Trial)
• Copyright: © 2022. The Author(s).

Chemical References

• Azetidines
• Benzyl Compounds
• siponimod

Topics

• Azetidines (pharmacology, therapeutic use)
• Benzyl Compounds (pharmacology, therapeutic use)
• Disease Progression
• Humans
• Magnetic Resonance Imaging
• Multiple Sclerosis (drug therapy)
• Multiple Sclerosis, Chronic Progressive (diagnostic imaging, drug therapy)
• Multiple Sclerosis, Relapsing-Remitting (drug therapy)