The EXPAND trial results supported the potential neuroprotective effects of siponimod.
Robert J. Fox, MD
Siponimod was shown to significantly reduce magnetic resonance imaging (MRI) lesion activity as well as slow brain volume loss in patients with secondary progressive multiple sclerosis (SPMS), according to the results of the EXPAND study.
The data was presented at MS Paris 2017, the joint meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) and the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
“These MRI results, together with the clinical outcomes of the study, support the overall beneficial effect of siponimod in patients with SPMS,” Robert Fox (pictured), MD, from the Mellen Centre for Treatment and Research in Multiple Sclerosis at Cleveland Clinic’s Neurological Institute. “[Additionally,] positive effects on brain volume loss and disability progression support the potential neuroprotective effects of siponimod.”
Data was given in a full analysis set (FAS), consisting of all patients and all available data regardless of early discontinuation, as well as a per-protocol set (PPS) which included all FAS patients lacking major deviations from protocol and consisted of all data up to the point of discontinuation.
An event- and exposure-driven study, EXPAND enrolled 1651 patients around the world, randomizing them to either once daily siponimod 2 mg (n=1105) or placebo (n=546). Patients with confirmed disability progression (CDP) were given the option to switch to open-label siponimod or other disease-modifying therapies while remaining in the core portion of the study.
“A key part of the contributions may come from the prevention of new lesions or discrete lesions, versus a direct neuroprotective effect on the brain,” Fox said. “I think a more sophisticated analysis would need to be done to kind of disentangle the direct inflammatory effects of siponimod on brain atrophy from the potential direct neuroprotective effects.”
In the FAS, there was a 75% decrease in T2 lesion volume for the siponimod group in the first 12 months from baseline 10286 mm3 (205 mm3 for the siponimod group compared to 818 mm3 with placebo), decreasing further to 83% by month 24 (163 mm3 with siponimod, 940 mm3 with placebo; p<0.001). In the PPS, the 12-month decrease in T2 lesion volume was 85%, followed by 94% in month 24 (108 mm3 siponimod, 880 mm3 with placebo).
Additionally, the number of new or enlarging T2 lesions was 1.00 in the siponimod group compared to 3.78 with placebo (73%; p<0.0001) in the FAS for the first 12 months, dropping to an average of 0.49 new lesions in month 24 for siponimod, compared to 3.44 with placebo. In the PPS, the decrease was also seen, with a mean of 0.74 new lesions in the siponimod group compared to 3.32 in the placebo group at 12 months, and an average of 0.31 with siponimod and 3.13 with placebo at 24 months.
The percentage of brain volume change in the FAS was -0.28 cm3 from 1421 cm3 baseline with siponimod and -0.46 cm3 from 1425 cm3 from baseline with placebo at month 12. As Fox noted, those effects continued through month 24, with an average reduction off -0.63 cm3 in the siponimod arm compared to -0.91 cm3 with placebo.
“Siponimod slowed brain volume loss in patients with SPMS as early as month 12 with the effects sustained to month 24,” Fox said. “The treatment benefits in favor of siponimod were observed for all key outcomes and analysis sets investigated.”