NDLI: Ponesimod, a selective S1P1 receptor modulator: a potential treatment for multiple sclerosis and other immune-mediated diseases

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Ponesimod, a selective S1P1 receptor modulator: a potential treatment for multiple sclerosis and other immune-mediated diseases

Content Provider	PubMed Central
Author	D’ambrosio, Daniele Freedman, Mark S. Prinz, Joerg
Copyright Year	2016
Abstract	The first oral treatment for relapsing multiple sclerosis, the nonselective sphingosine-1-phosphate receptor (S1PR) modulator fingolimod, led to identification of a pivotal role of sphingosine-1-phosphate and one of its five known receptors, S1P1R, in regulation of lymphocyte trafficking in multiple sclerosis. Modulation of S1P3R, initially thought to cause some of fingolimod’s side effects, prompted the search for novel compounds with high selectivity for S1P1R. Ponesimod is an orally active, selective S1P1R modulator that causes dose-dependent sequestration of lymphocytes in lymphoid organs. In contrast to the long half-life/slow elimination of fingolimod, ponesimod is eliminated within 1 week of discontinuation and its pharmacological effects are rapidly reversible. Clinical data in multiple sclerosis have shown a dose-dependent therapeutic effect of ponesimod and defined 20 mg as a daily dose with desired efficacy, and acceptable safety and tolerability. Phase II clinical data have also shown therapeutic efficacy of ponesimod in psoriasis. These findings have increased our understanding of psoriasis pathogenesis and suggest clinical utility of S1P1R modulation for treatment of various immune-mediated disorders. A gradual dose titration regimen was found to minimize the cardiac effects associated with initiation of ponesimod treatment. Selectivity for S1P1R, rapid onset and reversibility of pharmacological effects, and an optimized titration regimen differentiate ponesimod from fingolimod, and may lead to better safety and tolerability. Ponesimod is currently in phase III clinical development to assess efficacy and safety in relapsing multiple sclerosis. A phase II study is also ongoing to investigate the potential utility of ponesimod in chronic graft versus host disease.
Related Links	http://dx.doi.org/10.1177/2040622315617354
Starting Page	18
File Format	PDF
ISSN	20406231
e-ISSN	20406231
Journal	Therapeutic Advances in Chronic Disease
Issue Number	1
Volume Number	7
Language	English
Publisher	SAGE Publications
Publisher Date	2016-01-01
Access Restriction	Open
Rights Holder	SAGE Publications
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Medicine

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