Patients with a disease duration of
Findings from the phase 3 EXPAND trial of siponimod demonstrate a significantly greater reduction in risk for confirmed disability progression (CDP) at 3 and 6 months in patients with active secondary progressive multiple sclerosis (SPMS) with a disease duration of <16 years. The findings were presented at the 2020 America’s Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum, February 27-29, 2020, in West Palm Beach, Florida.
In March 2019, siponimod became the first FDA approved drug in more than a decade for the treatment of active SPMS. The approval was granted based on data from the EXPAND trial, which included 1600 patients with SPMS. Results from that trial demonstrated a 21% and 26% reduction in risk for 3- and 6-month CDP (P = .013), respectively.
Additionally, the drug, a selective sphingosine 1-phosphate receptor modulator, has been approved in the US for treatment of clinically isolated syndrome and relapsing-remitting MS.
In this sub-group, post hoc analyses, investigators sought to understand whether the efficacy of siponimod would change based on MS disease duration less than or greater than 16 years at baseline.
The primary end point was time to 3- and 6-month CDP measured using the Expanded Disability Status Scale (EDSS) scores. Adverse events (AEs), serious AEs, and AEs leading to treatment discontinuation were also assessed.
Among the 779 patients with active SPMS, 427 had an MS disease duration <16 years and 352 had an MS disease duration of >16 years. Of that, 285 and 231 were randomly assigned to receive 2 mg siponimod once daily, respectively.
In patients with an MS disease duration of <16 years, risk for 3- and 6-month CDP was reduced by 32.4% and 42.7%, respectively, compared with placebo (3 month: siponimod, n = 68 [23.9%]; placebo, n = 48 [33.8%]; HR 0.68; 95% CI, 0.47-0.98; P = .0378; 6 month: siponimod, n = 48 [16.8%]; placebo, n = 40 [28.2%]; HR 0.57; 95% CI, 0.38-0.87; P = .0093).
Among those with a disease duration ≥16 years at baseline, treatment with siponimod was associated with a trend towards reduced CDP risk of 31.9% and 27.1% at 3 and 6 months, respectively, compared with placebo (3 month: siponimod, n = 61 [26.4%]; placebo, n = 43 [35.5%]; HR 0.68; 95% CI, 0.46-1.01; P = .0540; 6 month, siponimod, n = 51 [22.1%]; placebo, n = 34 [28.1%]; HR 0.73; 95% CI, 0.47-1.13; P = .1544).
AEs in patients with <16 years of MS disease duration occurred in 84.9% and 75.4% in siponimod and placebo groups, respectively, compared with 89.2% and 81.8% of patients with MS disease duration ≥16 years in the siponimod and placebo groups, respectively.
The investigators concluded that the results may be reflective of the more advanced MS disease in patients with a disease duration of ≥16 years.
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Bar-Or A, Cohan SL, Coyle PK, Lublin FD, Meng X, Su W, Cree BA. Analysis of the effects of disease duration on the efficacy and safety of siponimod in patients with active SPMS from the Expand study. Presented at 2020 ACTRIMS Forum. February 27-29, 2020; West Palm Beach, FL. Abstract P030.