S1P Receptor Modulators in Multiple Sclerosis

EP: 1.S1P Receptor Modulators and the Treatment Landscape of Relapsing-Remitting Multiple Sclerosis

EP: 2.Tissue Selectivity of S1P Receptor Modulator

EP: 3.Safety Profile of S1P Receptor Modulators for Multiple Sclerosis

EP: 4.Monitoring Patients With Relapsing-Remitting Multiple Sclerosis on S1P Receptor Modulator

EP: 5.Switching Patients With Multiple Sclerosis to S1P Receptor Modulator

EP: 6.The Safety Data of Ozanimod in Multiple Sclerosis

EP: 7.The Safety of Other S1P Receptor Modulators in Multiple Sclerosis

EP: 8.Clinical Pearls for Treating Relapsing-Remitting Multiple Sclerosis With S1P Receptor Modulators

Now Viewing

EP: 9.S1P Receptor Modulators in Multiple Sclerosis

EP: 10.Selecting S1P Receptor Modulators in Multiple Sclerosis

EP: 11.Long-term Data With Ozanimod in Relapsing-Remitting Multiple Sclerosis

EP: 12.Long-Term Data With Other S1P Receptor Modulators in Multiple Sclerosis

EP: 13.Long-term Immunological Impact of Drug-Modifying Therapies in Multiple Sclerosis

EP: 14.Expert Advice on Multiple Sclerosis Treatment Cessation and Disease Rebound

EP: 15.Emerging Disease-Modifying Therapy Data in Multiple Sclerosis

EP: 16.Final Thoughts on S1P Receptor Modulators in Multiple Sclerosis

Transcript

Bruce Cree, MD, PhD, MAS: S1P [Multiple sclerosis, sphingosine-1-phosphate] receptor modulators address the fundamental biology of multiple sclerosis because of their critical roles in lymphocyte metabolism and in all of the dendrite, glial, and other central nervous system functions when it sees S1P receptors throughout the body. There are 5 different S1P receptors, and at least 2 or 3 of these have very important implications for multiple sclerosis.

There are 4 S1P receptor modulators that have received US FDA approval, and they are fingolimod, siponimod, ozanimod, and ponesimod. Now, each of these S1P receptor modulators has different specificity for the 5 different S1P receptors. There’s S1P1, S1P2, S1P3, S1P4, and S1P5. Fingolimod is the least selective; it does not have S1P2 activity, but it does have activity against S1P1 as well as S1P3, S1P4, and S1P5. Siponimod was designed to not have activity against S1P3 and S1P4, so it just interacts with the S1P1 and S1P5 receptors, as does ozanimod. That selectivity is important, as I’ll mention in a moment. The fourth S1P receptor modulator, ponesimod, has activity against only the S1P1 receptor. It is the most selective of the 4 approved S1P receptor modulators. Now, the extent of the activity against the different subtypes of these receptors, to some extent, determines some of the adverse events that are of interest. We do want the S1P1 receptors to be engaged because these are the receptors on lymphocytes and we believe that this is an important target for these S1P receptor modulators. We also think that S1P5 receptors within the central nervous system may be an important target as well that may potentially promote myelin repair. That may be a desirable target as well. However, S1P3 mediates a cardiac rhythm. Cardiac arrhythmias and complications associated with combined therapies of other drugs that may prolong the QT interval are potential problems for S1P receptor modulators that engage with S1P3 receptor. We don’t want to have S1P3 receptor activity, but we do want S1P1 and S1P5, and this might account for some of the different adverse events we see across these different S1P receptor modulators.

Transcript edited for clarity.