Assess the efficacy/safety profile of siponimod 2mg daily in a subgroup of patients with active SPMS from EXPAND who identified as Hispanic.

Siponimod significantly reduced 3-month and 6-month CDP risk by 31% and 37%, respectively, in patients with active SPMS from EXPAND. Minority group patients are underrepresented in clinical trials, resulting in limited data to inform decision-making.

Active SPMS was defined as having ≥1 relapse in the 2 years before Baseline and/or ≥1 T1 Gd+ lesion at Baseline. Proportional hazard and ANCOVA models were applied to analyze time to 3- and 6- month CDP (as per EDSS) and change in SDMT, respectively. Number and percentage of patients with AEs were reported.

Of 1651 patients in the overall EXPAND population, 106 (6.4%) identified as Hispanic, of which 40 had active SPMS (siponimod [n=31], placebo [n=9]). Mean (SD) age was 47.4 (7.6), 65.0% were female, mean (SD) duration since MS onset was 15.3 (6.4) years, mean (SD) baseline EDSS was 5.4 (1.1), and 77.5% of patients had ≥1 MS relapse in the last 2 years prior to Baseline. Siponimod reduced 3-month CDP risk by 42% (HR [95% CI]: 0.58 [0.17, 1.92]; p=0.37) and 6-month CDP risk by 67% (0.33 [0.07, 1.53], p=0.16) vs placebo. At Month-12, mean SDMT score changed minimally from Baseline for siponimod vs a 4.7-point worsening for placebo (difference between treatment groups, 4.9 (SE 2.6, p=0.07)). Rates of any AEs, SAEs, and AEs leading to discontinuation were similar for siponimod and placebo.

There was a numeric relative reduction in CDP risk in siponimod-treated patients with active SPMS identifying as Hispanic, consistent with the overall active SPMS cohort in EXPAND. Small sample size prevents us from drawing conclusions on statistical significance of the results in the Hispanic subgroup. This brings into focus the challenges of minority under-representation in clinical trials.