Fingolimod is an S1PR modulator and the first oral medication to be approved by the US Food and Drug Administration for the treatment of MS. Initially, fingolimod was used primarily as a second-line treatment for relapsing-remitting MS. As we became more comfortable with the side-effect profile of fingolimod, however, it began moving into the first-line treatment category for relapsing MS.

During the last several years, this particular space has become a bit more crowded with the introduction of several treatments that have a more selective effect on certain S1PRs. These newer approved S1PR modulators provide additional treatment options to our patients and include siponimod, ozanimod, and ponesimod. In general, this class of medications includes some of our best-tolerated MS treatments. With the more selective S1PR modulators, the cardiac effects have been somewhat diminished. And, for some patients, the 6-hour first-dose monitoring is no longer required, which is a major logistical benefit.

One advantage of this particular class of agents is that we have head-to-head comparisons in clinical trials demonstrating superior efficacy vs other DMTs. Compared with interferons, agents in the S1PR modulator class have demonstrated improvements in reducing the risk of relapse, sustained disability progression, the likelihood of new magnetic resonance imaging changes, the development of new T2 and Gd+ lesions, and the rate of whole brain and/or cortical and deep gray matter brain atrophy.

Current data suggest that siponimod and ozanimod have greater selectivity for S1PRs 1 and 5, whereas ponesimod has greater selectivity for S1PR 1. The extent to which these properties relate to differences in clinical efficacy are not yet known. The most robust data we have with these agents are in patients with relapsing forms of MS. Siponimod also carries an indication for active secondary progressive MS, where very few treatment options exist.