2021 CMSC Annual Meeting

Analyses of the Effect of Baseline Age on the Efficacy and Safety of Siponimod in Patients with Active Secondary Progressive Multiple Sclerosis from the Expand Study


Background: Siponimod is a selective S1P receptor (S1P1 and S1P5) modulator, approved in the USA for treatment of relapsing forms of MS, including clinically isolated syndrome, relapsing-remitting MS and active secondary progressive MS (SPMS). In the phase 3 EXPAND trial, for patients with active SPMS, siponimod significantly reduced risk of 3-month (primary endpoint) and 6-month confirmed disability progression (CDP) by 31% and 37% versus placebo, respectively. Objectives: Assess efficacy and safety of siponimod in patients with active SPMS in subgroups of patients aged <50 and ?50 years at Baseline from the EXPAND study. Methods: Post hoc analyses were performed in subgroups of patients aged <50 and ?50 years at Baseline with active SPMS, defined as having at least one relapse in the 2 years before Baseline and/or ?1 T1 gadolinium-enhancing lesion at Baseline, randomized to siponimod 2 mg daily or placebo. Proportional hazard model was used in the analysis of time to 3- and 6-month CDP (as per EDSS scores). Number and percentage of patients with adverse events (AEs) were reported. Analyses for hypothesis generation only. Results: There were 779 patients with active SPMS: 471 patients aged <50 years (siponimod, n=326; placebo, n=145) and 308 patients aged ?50 years (siponimod, n=190; placebo, n=118). In those <50 years, siponimod reduced risk of 3-month CDP by 30.5% compared with placebo (siponimod, n=87 (26.7%); placebo, n=52 (35.9%); hazard ratio (HR) (95% confidence interval (CI)): 0.70 (0.49 – 0.98); p=0.0383), and reduced 6-month CDP risk by 37.9% (siponimod, n=69 (21.2%); placebo, n=46 (31.7%); HR (95% CI): 0.62 (0.43 – 0.90); p=0.0126). In the subgroup of patients ?50 years, siponimod reduced the risk of 3-month and 6-month CDP by 37.7% and 37.4%, respectively, versus placebo (3-month: siponimod, n=42 (22.1%); placebo, n=39 (33.1%); HR (95% CI): 0.62 (0.40 – 0.96); p=0.0332; 6-month: siponimod, n=30 (15.8%); placebo, n=28 (23.7%); HR (95% CI): 0.63 (0.37 – 1.0); p=0.0749). Siponimod was generally well tolerated in both subgroups. Rates of any AE were similar for siponimod and placebo in patients <50 years (85.6% vs 80.0%), and slightly higher for siponimod in those ?50 years (88.9% vs 76.3%). Rates of serious AEs and AEs leading to discontinuation were similar between groups. Conclusions: Siponimod provided similar clinical benefits in reducing CDP risk in patients aged <50 years and ?50 years with active SPMS. In addition, these results are consistent with the overall active SPMS cohort in EXPAND.