This document contains information about sphingosine-1-phosphate receptor (S1PR) modulators that are approved or emerging treatments for multiple sclerosis. It provides a table showing the selectivity of fingolimod, ozanimod, siponimod, and ponesimod for different S1PR subtypes and their association with various cell types. It also summarizes the clinical profiles of fingolimod, ozanimod, siponimod and ponesimod based on clinical trial data, showing their effectiveness in treating relapsing or secondary progressive multiple sclerosis with generally favorable safety profiles.

1. S1PR
Subtype
Commonly
Associated
Cell Types
AV: atrioventricular; NK: natural killer; S1PR: sphingosine-1-phosphate receptor.
1. Chadury BZ, Cohen JA, Conway DS. Neurotherapeutics. 2017;14:859-873. 2. Subei AM, Cohen JA. CNS Drugs. 2015;29:565-575.
Access the activity, “Navigating the Expanding Sphingosine-1-Phosphate Receptor Modulator Armamentarium for Multiple Sclerosis Management:
Greater Opportunities for Patients With MS,” at www.peerview.com/TMC40.
S1PR1 S1PR2 S1PR3 S1PR4 S1PR5
Fingolimod
Lymphocytes Neurons
AV node and
conduction system
Endothelial
cells
Smooth
muscle
CNS NK cells
Ozanimod Siponimod Ponesimod
This Practice Aid has been provided as a quick reference to help learners apply the information to their daily practice and care of patients.
Selectivity of Approved and Emerging
Sphingosine-1-Phosphate Receptor Modulators1,2

2. IFN β-1a IM: intramuscular interferon β-1a; RRMS: relapsing-remitting multiple sclerosis; S1PR: sphingosine-1-phosphate receptor; SPMS: secondary-progressive multiple sclerosis.
1. Kappos L et al. N Engl J Med. 2010;362:387-401. 2. Calabresi PA et al. Lancet Neurol. 2014;13:545-556. 3. Cohen JA et al. N Engl J Med. 2010;362:402-415. 4. Cohen JA et al. 70th Annual Meeting of the American
Academy of Neurology (AAN 2018). Poster P3.410. 5. Comi G et al. AAN 2018. Poster P3.396. 6. Kappos L et al. Lancet. 2018;391:1263-1273. 7. Olsson T et al. J Neurol Neurosurg Psychiatry. 2014;85:1198-1208.
8. https://clinicaltrials.gov/ct2/show/NCT02907177. Accessed May 10, 2018. 9. https://clinicaltrials.gov/ct2/show/NCT02425644. Accessed May 10, 2018.
Access the activity, “Navigating the Expanding Sphingosine-1-Phosphate Receptor Modulator Armamentarium for
Multiple Sclerosis Management: Greater Opportunities for Patients With MS,” at www.peerview.com/TMC40.
Fingolimod1-3
Ozanimod4,5
Siponimod6
S1PR Modulator
Approved
Clinical Profile
Emerging
Superior to placebo in patients with RRMS in
FREEDOMS I and II trials
Superior to IFN β-1a IM in patients with RRMS
in TRANSFORMS trial
Superior to IFN β-1a IM in patients with RRMS
in RADIANCE Part B and SUNBEAM trials
Safety and tolerability profile favorable and
consistent between RADIANCE Part B
and SUNBEAM
Overall well tolerated, but first-dose and ongoing
monitoring required to mitigate potential
off-target effects
No patients had a second-degree or higher
AV block in either study
Superior to placebo in patients with SPMS in
the EXPAND trial
Superior to placebo on MRI endpoints in patients
with RRMS; beneficial effect also seen on
clinical endpoints
Overall well tolerated
Initial dose titration mitigated first-dose
cardiac effects
Phase 3 clinical trials are ongoing
Ponesimod7-9
This Practice Aid has been provided as a quick reference to help learners apply the information to their daily practice and care of patients.
Clinical Profiles of Approved and Emerging
S1PR Modulators for the Treatment of MS