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CNS Drugs
Published in: CNS Drugs 7/2015

01-07-2015 | Review Article

Sphingosine 1-Phosphate Receptor Modulators in Multiple Sclerosis

Authors: Adnan M. Subei, Jeffrey A. Cohen

Published in: CNS Drugs | Issue 7/2015

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Abstract

Sphingosine 1-phosphate (S1P) receptor modulators possess a unique mechanism of action as disease-modifying therapy for multiple sclerosis (MS). Subtype 1 S1P receptors are expressed on the surfaces of lymphocytes and are important in regulating egression from lymph nodes. The S1P receptor modulators indirectly antagonize the receptor’s function and sequester lymphocytes in lymph nodes. Fingolimod was the first S1P agent approved in the USA in 2010 for relapsing MS after two phase III trials (FREEDOMS and TRANSFORMS) demonstrated potent efficacy, and good safety and tolerability. Post-marketing experience, as well as a third phase III trial (FREEDOMS II), also showed favorable results. More selective S1P receptor agents—ponesimod (ACT128800), siponimod (BAF312), ozanimod (RPC1063), ceralifimod (ONO-4641), GSK2018682, and MT-1303—are still in relatively early stages of development, but phase I and II trials showed promising efficacy and safety. However, these observations have yet to be reproduced in phase III clinical trials.
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Metadata
Title
Sphingosine 1-Phosphate Receptor Modulators in Multiple Sclerosis
Authors
Adnan M. Subei
Jeffrey A. Cohen
Publication date
01-07-2015
Publisher
Springer International Publishing
Published in
CNS Drugs / Issue 7/2015
Print ISSN: 1172-7047
Electronic ISSN: 1179-1934
DOI
https://doi.org/10.1007/s40263-015-0261-z

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