Siponimod (BAF312) is a synthetic molecule belonging to the 
sphingosine-1-phosphate (S1P) modulator family, which has putative 
neuroprotective properties and well-characterized immunomodulating effects 
mediated by sequestration of B and T cells in secondary lymphoid organs. 
Compared to fingolimod (ie, precursor of the S1P modulators commercially 
available for the treatment of relapsing-remitting [RR] multiple sclerosis 
[MS]), siponimod exhibits selective affinity for types 1 and 5 S1P receptor, 
leading to a lower risk of adverse events that are mainly induced by S1P3 
receptor activation, such as bradycardia and vasoconstriction. In addition, S1P1 
and S1P5 receptors are expressed by neurons and glia and could mediate a 
possible neuroprotective effect of the drug. A Phase II clinical trial of 
siponimod for RR MS showed a significant effect of the active drug compared to 
placebo on reducing gadolinium-enhancing lesions on brain magnetic resonance 
imaging (MRI) after 3 months of treatment. In a recently completed Phase III 
trial, treatment with siponimod was associated with a significant reduction in 
disability progression in secondary progressive (SP) MS patients compared to 
placebo. In this article, current evidence supporting siponimod efficacy for SP 
MS is reviewed.