Phase 3 Clinical Trial Shows Siponimod Significantly Improved Outcomes in Patients With Secondary Progressive Multiple Sclerosis
Results from the phase 3 clinical trial, EXPAND, studying oral, once-daily siponimod (Novartis; East Hanover, NJ) for treatment of secondary progressive multiple sclerosis (SPMS) were published today (Lancet. 2018; published online March 22.) Pivotal results include delayed disability progression, reduced frequency of relapses, and decreased disease activity on MRI including loss of brain volume. Siponimod is an investigational selective modulator of specific subtypes of the sphingosine-1-phosphate (S1P) receptor.
Treatment of patients with SPMS with siponimod for 3 months reduced the risk of disability progression by 21% compared to those treated with placebo (P = .013) and meaningfully delayed the risk of confirmed disability progression at the 6-month checkpoint by 26% versus progression in subjects treated with placebo (P = .006). The annualized relapse rate was reduced by 55% in patients treated with siponimod vs those treated with placebo (P = .0001). The secondary endpoint of a significant difference in the timed-25-foot walk test and the MS walking scale were not met.
On MRI of patients treated with siponimod, the increase of T2 leasions was limited by 80% measured by volume change from baseline versus the mean over 12 and 24 months (P < .0001) and the rate of brain volume loss was slowed by 23% (relative difference; mean across 12 and 24 months (P = .0002).
If approved, siponimod will be the first disease-modifying therapy for patients with SPMS, many of whom have nonrelapsing disease and significant disability.
"Today's published full EXPAND results show that siponimod can delay disability progression in typical established SPMS patients, where other approaches tested so far have been unsuccessful," said Professor Ludwig Kappos, University Hospital Basel and Principal Investigator of EXPAND. "These data are all the more impressive when considering that the majority of patients had already advanced disability when starting treatment in EXPAND."