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Last updated: 3 Mar 2016

Siponimod

Summary
Class: 
Immunomodulator
(1)
The selective sphingosine 1-phosphate receptor modulator BAF312 redirects lymphocyte distribution and has species-specific effects on heart rate.
Gergely P, Nuesslein-Hildesheim B, Guerini D, Brinkmann V, Traebert M, Bruns C, Pan S, Gray NS, Hinterding K, Cooke NG, et al.
Br J Pharmacol. 2012 Nov; 167(5):1035-47. PMID: 22646698. Abstract
Target: 
Sphingosine 1-phosphate (S1P) receptor subtypes S1P1 and S1P5
(1)
The selective sphingosine 1-phosphate receptor modulator BAF312 redirects lymphocyte distribution and has species-specific effects on heart rate.
Gergely P, Nuesslein-Hildesheim B, Guerini D, Brinkmann V, Traebert M, Bruns C, Pan S, Gray NS, Hinterding K, Cooke NG, et al.
Br J Pharmacol. 2012 Nov; 167(5):1035-47. PMID: 22646698. Abstract
B cell distrubution
(1)
The selective sphingosine 1-phosphate receptor modulator BAF312 redirects lymphocyte distribution and has species-specific effects on heart rate.
Gergely P, Nuesslein-Hildesheim B, Guerini D, Brinkmann V, Traebert M, Bruns C, Pan S, Gray NS, Hinterding K, Cooke NG, et al.
Br J Pharmacol. 2012 Nov; 167(5):1035-47. PMID: 22646698. Abstract
T cell distribution
(1)
The selective sphingosine 1-phosphate receptor modulator BAF312 redirects lymphocyte distribution and has species-specific effects on heart rate.
Gergely P, Nuesslein-Hildesheim B, Guerini D, Brinkmann V, Traebert M, Bruns C, Pan S, Gray NS, Hinterding K, Cooke NG, et al.
Br J Pharmacol. 2012 Nov; 167(5):1035-47. PMID: 22646698. Abstract
Status for MS: 
Phase III trial is underway as of July, 2013
(3)
Exploring the Efficacy and Safety of Siponimod in Patients With Secondary Progressive Multiple Sclerosis (EXPAND)
ClinicalTrials.gov, 29 Jul 2013
Accessed on 11 Aug 2013 from http://www.clinicaltrials.gov/ct2/show/NCT01665144.
Administration: 
Oral
(1)
The selective sphingosine 1-phosphate receptor modulator BAF312 redirects lymphocyte distribution and has species-specific effects on heart rate.
Gergely P, Nuesslein-Hildesheim B, Guerini D, Brinkmann V, Traebert M, Bruns C, Pan S, Gray NS, Hinterding K, Cooke NG, et al.
Br J Pharmacol. 2012 Nov; 167(5):1035-47. PMID: 22646698. Abstract
Commercial: 
Clinical trials have been sponsored by Novartis Pharma
(1)
The selective sphingosine 1-phosphate receptor modulator BAF312 redirects lymphocyte distribution and has species-specific effects on heart rate.
Gergely P, Nuesslein-Hildesheim B, Guerini D, Brinkmann V, Traebert M, Bruns C, Pan S, Gray NS, Hinterding K, Cooke NG, et al.
Br J Pharmacol. 2012 Nov; 167(5):1035-47. PMID: 22646698. Abstract
(4)
Siponimod (BAF312) for the Treatment of Secondary Progressive Multiple Sclerosis: Design of the Phase 3 EXPAND Trial
Kappos L, Bar-Or A, Cree B, Fox R, Giovannoni G, Gold R, Vermersch P, Lam E, Pohlmann H, Zhang-Auberson L, et al., Neurology (Meeting Abstracts), 12 Feb 2013
Accessed on 11 Aug 2013 from http://www.neurology.org/cgi/content/meeting_abstract/80/1_MeetingAbstracts/P07.126.
(9)
Dose titration of BAF312 attenuates the initial heart rate reducing effect in healthy subjects.
Legangneux E, Gardin A, Johns D
Br J Clin Pharmacol. 2013 Mar; 75(3):831-41. PMID: 22845008. Abstract
(10)
Siponimod for patients with relapsing-remitting multiple sclerosis (BOLD): an adaptive, dose-ranging, randomised, phase 2 study.
Selmaj K, Li DKB, Hartung H-P, Hemmer B, Kappos L, Freedman MS, Stüve O, Rieckmann P, Montalban X, Ziemssen T, et al.
Lancet Neurol. 2013 Aug; 12(8):756-67. Epub 2013 Jun 11. PMID: 23764350. Abstract
(11)
Long-term Safety, Tolerability and Efficacy of BAF312 Given Orally in Patients With Relapsing-remitting Multiple Sclerosis
ClinicalTrials.gov, 18 Jan 2013
Accessed on 11 Aug 2013 from http://www.clinicaltrials.gov/ct2/show/NCT01185821.
Names
Name: 
Siponimod
Synonyms: 
BAF312
(1)
The selective sphingosine 1-phosphate receptor modulator BAF312 redirects lymphocyte distribution and has species-specific effects on heart rate.
Gergely P, Nuesslein-Hildesheim B, Guerini D, Brinkmann V, Traebert M, Bruns C, Pan S, Gray NS, Hinterding K, Cooke NG, et al.
Br J Pharmacol. 2012 Nov; 167(5):1035-47. PMID: 22646698. Abstract
(4)
Siponimod (BAF312) for the Treatment of Secondary Progressive Multiple Sclerosis: Design of the Phase 3 EXPAND Trial
Kappos L, Bar-Or A, Cree B, Fox R, Giovannoni G, Gold R, Vermersch P, Lam E, Pohlmann H, Zhang-Auberson L, et al., Neurology (Meeting Abstracts), 12 Feb 2013
Accessed on 11 Aug 2013 from http://www.neurology.org/cgi/content/meeting_abstract/80/1_MeetingAbstracts/P07.126.
BAF 312
(2)
ChemIDplus Advanced
United States National Library of Medicine
Accessed on 29 Jul 2013 from http://chem.sis.nlm.nih.gov/chemidplus/chemidheavy.jsp.
UNII-RR6P8L282I
(2)
ChemIDplus Advanced
United States National Library of Medicine
Accessed on 29 Jul 2013 from http://chem.sis.nlm.nih.gov/chemidplus/chemidheavy.jsp.
Systematic name: 
(1-(4-{1-[(E)-4-cyclohexyl-3-trifluoromethylbenzyloxyimino]-ethyl}-2-ethylbenzyl)-azetidine-3-carboxylic acid)
(1)
The selective sphingosine 1-phosphate receptor modulator BAF312 redirects lymphocyte distribution and has species-specific effects on heart rate.
Gergely P, Nuesslein-Hildesheim B, Guerini D, Brinkmann V, Traebert M, Bruns C, Pan S, Gray NS, Hinterding K, Cooke NG, et al.
Br J Pharmacol. 2012 Nov; 167(5):1035-47. PMID: 22646698. Abstract
Physiology
Class: 
Immunomodulator
(1)
The selective sphingosine 1-phosphate receptor modulator BAF312 redirects lymphocyte distribution and has species-specific effects on heart rate.
Gergely P, Nuesslein-Hildesheim B, Guerini D, Brinkmann V, Traebert M, Bruns C, Pan S, Gray NS, Hinterding K, Cooke NG, et al.
Br J Pharmacol. 2012 Nov; 167(5):1035-47. PMID: 22646698. Abstract
Target: 
Sphingosine 1-phosphate (S1P) receptor subtypes S1P1 and S1P5
(1)
The selective sphingosine 1-phosphate receptor modulator BAF312 redirects lymphocyte distribution and has species-specific effects on heart rate.
Gergely P, Nuesslein-Hildesheim B, Guerini D, Brinkmann V, Traebert M, Bruns C, Pan S, Gray NS, Hinterding K, Cooke NG, et al.
Br J Pharmacol. 2012 Nov; 167(5):1035-47. PMID: 22646698. Abstract
B cell distrubution
(1)
The selective sphingosine 1-phosphate receptor modulator BAF312 redirects lymphocyte distribution and has species-specific effects on heart rate.
Gergely P, Nuesslein-Hildesheim B, Guerini D, Brinkmann V, Traebert M, Bruns C, Pan S, Gray NS, Hinterding K, Cooke NG, et al.
Br J Pharmacol. 2012 Nov; 167(5):1035-47. PMID: 22646698. Abstract
T cell distribution
(1)
The selective sphingosine 1-phosphate receptor modulator BAF312 redirects lymphocyte distribution and has species-specific effects on heart rate.
Gergely P, Nuesslein-Hildesheim B, Guerini D, Brinkmann V, Traebert M, Bruns C, Pan S, Gray NS, Hinterding K, Cooke NG, et al.
Br J Pharmacol. 2012 Nov; 167(5):1035-47. PMID: 22646698. Abstract
Properties: 
Derivative of fingolimod
(1)
The selective sphingosine 1-phosphate receptor modulator BAF312 redirects lymphocyte distribution and has species-specific effects on heart rate.
Gergely P, Nuesslein-Hildesheim B, Guerini D, Brinkmann V, Traebert M, Bruns C, Pan S, Gray NS, Hinterding K, Cooke NG, et al.
Br J Pharmacol. 2012 Nov; 167(5):1035-47. PMID: 22646698. Abstract
Half-maximal effective concentration values for sphingosine 1-phosphate receptor subtypes S1P1 and S1P5 are in the sub-nanomolar range (0.39 nM and 0.98 nM, respectively)
(1)
The selective sphingosine 1-phosphate receptor modulator BAF312 redirects lymphocyte distribution and has species-specific effects on heart rate.
Gergely P, Nuesslein-Hildesheim B, Guerini D, Brinkmann V, Traebert M, Bruns C, Pan S, Gray NS, Hinterding K, Cooke NG, et al.
Br J Pharmacol. 2012 Nov; 167(5):1035-47. PMID: 22646698. Abstract
Steady-state concentrations are reached after 6 days of once-daily administration in healthy individuals
(1)
The selective sphingosine 1-phosphate receptor modulator BAF312 redirects lymphocyte distribution and has species-specific effects on heart rate.
Gergely P, Nuesslein-Hildesheim B, Guerini D, Brinkmann V, Traebert M, Bruns C, Pan S, Gray NS, Hinterding K, Cooke NG, et al.
Br J Pharmacol. 2012 Nov; 167(5):1035-47. PMID: 22646698. Abstract
Effective elimination half-life is 22 to 38 hours in healthy individuals
(1)
The selective sphingosine 1-phosphate receptor modulator BAF312 redirects lymphocyte distribution and has species-specific effects on heart rate.
Gergely P, Nuesslein-Hildesheim B, Guerini D, Brinkmann V, Traebert M, Bruns C, Pan S, Gray NS, Hinterding K, Cooke NG, et al.
Br J Pharmacol. 2012 Nov; 167(5):1035-47. PMID: 22646698. Abstract
Complete wash-out after treatment is discontinued is predicted to take about 6.3 days
(1)
The selective sphingosine 1-phosphate receptor modulator BAF312 redirects lymphocyte distribution and has species-specific effects on heart rate.
Gergely P, Nuesslein-Hildesheim B, Guerini D, Brinkmann V, Traebert M, Bruns C, Pan S, Gray NS, Hinterding K, Cooke NG, et al.
Br J Pharmacol. 2012 Nov; 167(5):1035-47. PMID: 22646698. Abstract
Potency against the sphingosine-1-phosphate (S1P) receptor subtype S1P1, selectivity against other S1P receptors, and species cross-reactivity have been compared for multiple S1P1 receptor agonists (including fingolimod, siponimod, and CS-0777)
(12)
No Differences Observed among Multiple Clinical S1P1 Receptor Agonists (Functional Antagonists) in S1P1 Receptor Down-regulation and Degradation.
Lukas S, Patnaude L, Haxhinasto S, Slavin A, Hill-Drzewi M, Horan J, Modis L K
J Biomol Screen. 2013 Sep 3. PMID: 24003058. Abstract
Multiple sphingosine-1-phosphate (S1P) receptor subtype S1P1 agonists (including fingolimod, siponimod, and CS-0777) all signal identically through the S1P1 receptor, causing receptor degradation
(12)
No Differences Observed among Multiple Clinical S1P1 Receptor Agonists (Functional Antagonists) in S1P1 Receptor Down-regulation and Degradation.
Lukas S, Patnaude L, Haxhinasto S, Slavin A, Hill-Drzewi M, Horan J, Modis L K
J Biomol Screen. 2013 Sep 3. PMID: 24003058. Abstract

Mechanisms/Effects

Human: 
Predicted to prevent lymphocyte egress from the lymph nodes and thymus, a process that requires sphingosine 1-phosphate (S1P) subtype 1 receptors, by causing the internalization of these receptors so that they cannot respond to S1P
(1)
The selective sphingosine 1-phosphate receptor modulator BAF312 redirects lymphocyte distribution and has species-specific effects on heart rate.
Gergely P, Nuesslein-Hildesheim B, Guerini D, Brinkmann V, Traebert M, Bruns C, Pan S, Gray NS, Hinterding K, Cooke NG, et al.
Br J Pharmacol. 2012 Nov; 167(5):1035-47. PMID: 22646698. Abstract
Selective agonist for sphingosine 1-phosphate (S1P) receptor subtypes S1P1 and S1P5
(1)
The selective sphingosine 1-phosphate receptor modulator BAF312 redirects lymphocyte distribution and has species-specific effects on heart rate.
Gergely P, Nuesslein-Hildesheim B, Guerini D, Brinkmann V, Traebert M, Bruns C, Pan S, Gray NS, Hinterding K, Cooke NG, et al.
Br J Pharmacol. 2012 Nov; 167(5):1035-47. PMID: 22646698. Abstract
Selectivity for sphingosine 1-phosphate (S1P) receptor subtype S1P1 is more than 1000-fold greater than for receptor subtypes S1P2, S1P3, and S1P4
(1)
The selective sphingosine 1-phosphate receptor modulator BAF312 redirects lymphocyte distribution and has species-specific effects on heart rate.
Gergely P, Nuesslein-Hildesheim B, Guerini D, Brinkmann V, Traebert M, Bruns C, Pan S, Gray NS, Hinterding K, Cooke NG, et al.
Br J Pharmacol. 2012 Nov; 167(5):1035-47. PMID: 22646698. Abstract
Promotes internalization of sphingosine 1-phosphate (S1P1) receptors to a greater extent than S1P itself, as shown in experiments in which human S1P1 receptors were expressed in Chinese hamster ovary cells
(1)
The selective sphingosine 1-phosphate receptor modulator BAF312 redirects lymphocyte distribution and has species-specific effects on heart rate.
Gergely P, Nuesslein-Hildesheim B, Guerini D, Brinkmann V, Traebert M, Bruns C, Pan S, Gray NS, Hinterding K, Cooke NG, et al.
Br J Pharmacol. 2012 Nov; 167(5):1035-47. PMID: 22646698. Abstract
Promotes internalization of sphingosine 1-phosphate (S1P1) receptors, which largely remain internal up to 12 hours after the compound is removed, whereas receptors that are internalized by S1P treatment return to the cell surface within 3 hours, as shown in experiments in which human S1P1 receptors were expressed in Chinese hamster ovary cells
(1)
The selective sphingosine 1-phosphate receptor modulator BAF312 redirects lymphocyte distribution and has species-specific effects on heart rate.
Gergely P, Nuesslein-Hildesheim B, Guerini D, Brinkmann V, Traebert M, Bruns C, Pan S, Gray NS, Hinterding K, Cooke NG, et al.
Br J Pharmacol. 2012 Nov; 167(5):1035-47. PMID: 22646698. Abstract
Reduces the peripheral absolute lymphocyte count in a dose-dependent, reversible manner in healthy individuals
(1)
The selective sphingosine 1-phosphate receptor modulator BAF312 redirects lymphocyte distribution and has species-specific effects on heart rate.
Gergely P, Nuesslein-Hildesheim B, Guerini D, Brinkmann V, Traebert M, Bruns C, Pan S, Gray NS, Hinterding K, Cooke NG, et al.
Br J Pharmacol. 2012 Nov; 167(5):1035-47. PMID: 22646698. Abstract
Strongly reduces peripheral levels of both B and T cells, with CD4+ T cells affected more than CD8+ T cells, but does not affect monocyte levels, in healthy individuals
(1)
The selective sphingosine 1-phosphate receptor modulator BAF312 redirects lymphocyte distribution and has species-specific effects on heart rate.
Gergely P, Nuesslein-Hildesheim B, Guerini D, Brinkmann V, Traebert M, Bruns C, Pan S, Gray NS, Hinterding K, Cooke NG, et al.
Br J Pharmacol. 2012 Nov; 167(5):1035-47. PMID: 22646698. Abstract
Reduces peripheral levels of naïve and central memory (CCR7+) CD4+ T cells more than peripheral effector memory (CCR7-) CD4+ T cells in healthy individuals
(1)
The selective sphingosine 1-phosphate receptor modulator BAF312 redirects lymphocyte distribution and has species-specific effects on heart rate.
Gergely P, Nuesslein-Hildesheim B, Guerini D, Brinkmann V, Traebert M, Bruns C, Pan S, Gray NS, Hinterding K, Cooke NG, et al.
Br J Pharmacol. 2012 Nov; 167(5):1035-47. PMID: 22646698. Abstract
Activates G-protein-coupled inwardly rectifying potassium channels in human atrial myocytes (indicating the potential for reducing heart rate transiently); the effect is about 8 times less potent than that of S1P itself
(1)
The selective sphingosine 1-phosphate receptor modulator BAF312 redirects lymphocyte distribution and has species-specific effects on heart rate.
Gergely P, Nuesslein-Hildesheim B, Guerini D, Brinkmann V, Traebert M, Bruns C, Pan S, Gray NS, Hinterding K, Cooke NG, et al.
Br J Pharmacol. 2012 Nov; 167(5):1035-47. PMID: 22646698. Abstract
Causes a transient reduction in heart rate after the first dose
(1)
The selective sphingosine 1-phosphate receptor modulator BAF312 redirects lymphocyte distribution and has species-specific effects on heart rate.
Gergely P, Nuesslein-Hildesheim B, Guerini D, Brinkmann V, Traebert M, Bruns C, Pan S, Gray NS, Hinterding K, Cooke NG, et al.
Br J Pharmacol. 2012 Nov; 167(5):1035-47. PMID: 22646698. Abstract
Activates pERK, pAKT, and Ca2+ signaling in human astrocytes
(16)
The dual S1PR1/S1PR5 drug BAF312 (Siponimod) attenuates demyelination in organotypic slice cultures.
O'Sullivan C, Schubart A, Mir AK, Dev KK
J Neuroinflammation. 2016; 13(1):31. Epub 2016 Feb 08. PMID: 26856814. Abstract
Does not reduce levels of interleukin 6 (IL-6) produced by human astrocyte cultures treated with tumor necrosis factor alpha and IL-17
(16)
The dual S1PR1/S1PR5 drug BAF312 (Siponimod) attenuates demyelination in organotypic slice cultures.
O'Sullivan C, Schubart A, Mir AK, Dev KK
J Neuroinflammation. 2016; 13(1):31. Epub 2016 Feb 08. PMID: 26856814. Abstract
Fingolimod directly inhibits the human ether-a-go-go-related gene (hERG) current, whereas siponimod does not, in a model in which hERG channels are expressed in human embryonic kidney 293 cells
(13)
Analysis of Onset Mechanisms of a Sphingosine 1-Phosphate Receptor Modulator Fingolomod-Induced Atrioventricular Conduction Block and QT-Interval Prolongation.
Yagi Y, Nakamura Y, Kitahara K, Harada T, Kato K, Ninomiya T, Cao X, Ohara H, Izumi-Nakaseko H, Suzuki K, et al.
Toxicol Appl Pharmacol. 2014 Sep 16. PMID: 25223691. Abstract
Animal: 
Suppresses previously established neurological deficits in a Dark Agouti rat model of chronic experimental autoimmune encephalomyelitis
(1)
The selective sphingosine 1-phosphate receptor modulator BAF312 redirects lymphocyte distribution and has species-specific effects on heart rate.
Gergely P, Nuesslein-Hildesheim B, Guerini D, Brinkmann V, Traebert M, Bruns C, Pan S, Gray NS, Hinterding K, Cooke NG, et al.
Br J Pharmacol. 2012 Nov; 167(5):1035-47. PMID: 22646698. Abstract
Increases levels of myelin basic protein, promoting remyelination, after a transient treatment that causes demyelination in cultures prepared from fetal rat telencephalon
(5)
Fingolimod modulates microglial activation to augment markers of remyelination.
Jackson SJ, Giovannoni G, Baker D
J Neuroinflammation. 2011; 8:76. Epub 2011 Jul 05. PMID: 21729281. Abstract
Activates pERK and pAKT signaling and causes internalization of the sphingosine-1 phosphate receptor 1 in mouse astrocytes
(16)
The dual S1PR1/S1PR5 drug BAF312 (Siponimod) attenuates demyelination in organotypic slice cultures.
O'Sullivan C, Schubart A, Mir AK, Dev KK
J Neuroinflammation. 2016; 13(1):31. Epub 2016 Feb 08. PMID: 26856814. Abstract
Moderately reduces levels of interleukin 6 produced by mouse astrocyte or microglia cultures treated with lipopolysaccharide
(16)
The dual S1PR1/S1PR5 drug BAF312 (Siponimod) attenuates demyelination in organotypic slice cultures.
O'Sullivan C, Schubart A, Mir AK, Dev KK
J Neuroinflammation. 2016; 13(1):31. Epub 2016 Feb 08. PMID: 26856814. Abstract
Reduces demyelination induced by lysophosphatidylcholine or the Krabbe disease metabolite psychosine in mouse cerebellar slice cultures
(16)
The dual S1PR1/S1PR5 drug BAF312 (Siponimod) attenuates demyelination in organotypic slice cultures.
O'Sullivan C, Schubart A, Mir AK, Dev KK
J Neuroinflammation. 2016; 13(1):31. Epub 2016 Feb 08. PMID: 26856814. Abstract
Causes acute bradycardia in anesthetized rats, as shown in an experiment involving acute intravenous drug infusion
(6)
The clinically-tested S1P receptor agonists, FTY720 and BAF312, demonstrate subtype-specific bradycardia (S1P₁) and hypertension (S1P₃) in rat.
Fryer RM, Muthukumarana A, Harrison PC, Nodop Mazurek S, Chen R R, Harrington KE, Dinallo RM, Horan JC, Patnaude L, Modis LK, et al.
PLoS One. 2012; 7(12):e52985. Epub 2012 Dec 28. PMID: 23285242. Abstract
Unlike fingolimod, does not affect blood pressure in rats
(6)
The clinically-tested S1P receptor agonists, FTY720 and BAF312, demonstrate subtype-specific bradycardia (S1P₁) and hypertension (S1P₃) in rat.
Fryer RM, Muthukumarana A, Harrison PC, Nodop Mazurek S, Chen R R, Harrington KE, Dinallo RM, Horan JC, Patnaude L, Modis LK, et al.
PLoS One. 2012; 7(12):e52985. Epub 2012 Dec 28. PMID: 23285242. Abstract
Reduces levels of circulating monocytes and lymphocytes over a similar time course, as shown by experiments in rats and mice
(7)
Circulating monocytes are reduced by sphingosine-1-phosphate receptor modulators independently of S1P3.
Lewis ND, Haxhinasto SA, Anderson SM, Stefanopoulos DE, Fogal SE, Adusumalli P, Desai SN, Patnaude LA, Lukas SM, Ryan KR, et al.
J Immunol. 2013 Apr 1; 190(7):3533-40. Epub 2013 Feb 22. PMID: 23436932. Abstract
Reduces levels of circulating monocytes and increases the total number of monocytes in bone marrow and spleen in rats and mice
(7)
Circulating monocytes are reduced by sphingosine-1-phosphate receptor modulators independently of S1P3.
Lewis ND, Haxhinasto SA, Anderson SM, Stefanopoulos DE, Fogal SE, Adusumalli P, Desai SN, Patnaude LA, Lukas SM, Ryan KR, et al.
J Immunol. 2013 Apr 1; 190(7):3533-40. Epub 2013 Feb 22. PMID: 23436932. Abstract
Both fingolimod and siponimod induce atrioventricular conduction block at high dose, whereas fingolimod but not siponimod prolongs the QT interval at high dose and siponimod but not fingolimod prolongs the PR interval at low dose, in a guinea-pig model
(13)
Analysis of Onset Mechanisms of a Sphingosine 1-Phosphate Receptor Modulator Fingolomod-Induced Atrioventricular Conduction Block and QT-Interval Prolongation.
Yagi Y, Nakamura Y, Kitahara K, Harada T, Kato K, Ninomiya T, Cao X, Ohara H, Izumi-Nakaseko H, Suzuki K, et al.
Toxicol Appl Pharmacol. 2014 Sep 16. PMID: 25223691. Abstract
Regulatory and Commercial Status
Status for MS: 
Phase III trial is underway as of July, 2013
(3)
Exploring the Efficacy and Safety of Siponimod in Patients With Secondary Progressive Multiple Sclerosis (EXPAND)
ClinicalTrials.gov, 29 Jul 2013
Accessed on 11 Aug 2013 from http://www.clinicaltrials.gov/ct2/show/NCT01665144.
Highest status achieved (for any condition): 
Phase III
(3)
Exploring the Efficacy and Safety of Siponimod in Patients With Secondary Progressive Multiple Sclerosis (EXPAND)
ClinicalTrials.gov, 29 Jul 2013
Accessed on 11 Aug 2013 from http://www.clinicaltrials.gov/ct2/show/NCT01665144.
Other uses: 
Effectiveness in polymyositis (a chronic inflammatory condition of muscles) is being tested in a Phase II trial (as of May, 2013)
(8)
Efficacy and Tolerability of BAF312 in Patients With Polymyositis
ClinicalTrials.gov, 10 May 2013
Accessed on 11 Aug 2013 from http://www.clinicaltrials.gov/ct2/show/NCT01801917.
Administration: 
Oral
(1)
The selective sphingosine 1-phosphate receptor modulator BAF312 redirects lymphocyte distribution and has species-specific effects on heart rate.
Gergely P, Nuesslein-Hildesheim B, Guerini D, Brinkmann V, Traebert M, Bruns C, Pan S, Gray NS, Hinterding K, Cooke NG, et al.
Br J Pharmacol. 2012 Nov; 167(5):1035-47. PMID: 22646698. Abstract
Negative effects: 
Initiation of treatment in an individual with SPMS was followed by acute optic neuritis in one eye; visual function was not regained after siponimod discontinuation and corticosteroid treatment
(17)
Acute relapse after initiation of Siponimod in a patient with secondary progressive MS.
Hussain R, O'Leary S, Pacheco FM, Zacharias TE, Litvak P, Sguigna P, Marder E, Kia K, Kooner K, Stüve O
J Neurol. 2016 Mar; 263(3):606-10. Epub 2016 Feb 25. PMID: 26914924. Abstract
Dizziness
(1)
The selective sphingosine 1-phosphate receptor modulator BAF312 redirects lymphocyte distribution and has species-specific effects on heart rate.
Gergely P, Nuesslein-Hildesheim B, Guerini D, Brinkmann V, Traebert M, Bruns C, Pan S, Gray NS, Hinterding K, Cooke NG, et al.
Br J Pharmacol. 2012 Nov; 167(5):1035-47. PMID: 22646698. Abstract
Headache
(1)
The selective sphingosine 1-phosphate receptor modulator BAF312 redirects lymphocyte distribution and has species-specific effects on heart rate.
Gergely P, Nuesslein-Hildesheim B, Guerini D, Brinkmann V, Traebert M, Bruns C, Pan S, Gray NS, Hinterding K, Cooke NG, et al.
Br J Pharmacol. 2012 Nov; 167(5):1035-47. PMID: 22646698. Abstract
Elevations in liver enzymes (generally not significant clinically)
(1)
The selective sphingosine 1-phosphate receptor modulator BAF312 redirects lymphocyte distribution and has species-specific effects on heart rate.
Gergely P, Nuesslein-Hildesheim B, Guerini D, Brinkmann V, Traebert M, Bruns C, Pan S, Gray NS, Hinterding K, Cooke NG, et al.
Br J Pharmacol. 2012 Nov; 167(5):1035-47. PMID: 22646698. Abstract
Commercial: 
Clinical trials have been sponsored by Novartis Pharma
(1)
The selective sphingosine 1-phosphate receptor modulator BAF312 redirects lymphocyte distribution and has species-specific effects on heart rate.
Gergely P, Nuesslein-Hildesheim B, Guerini D, Brinkmann V, Traebert M, Bruns C, Pan S, Gray NS, Hinterding K, Cooke NG, et al.
Br J Pharmacol. 2012 Nov; 167(5):1035-47. PMID: 22646698. Abstract
(4)
Siponimod (BAF312) for the Treatment of Secondary Progressive Multiple Sclerosis: Design of the Phase 3 EXPAND Trial
Kappos L, Bar-Or A, Cree B, Fox R, Giovannoni G, Gold R, Vermersch P, Lam E, Pohlmann H, Zhang-Auberson L, et al., Neurology (Meeting Abstracts), 12 Feb 2013
Accessed on 11 Aug 2013 from http://www.neurology.org/cgi/content/meeting_abstract/80/1_MeetingAbstracts/P07.126.
(9)
Dose titration of BAF312 attenuates the initial heart rate reducing effect in healthy subjects.
Legangneux E, Gardin A, Johns D
Br J Clin Pharmacol. 2013 Mar; 75(3):831-41. PMID: 22845008. Abstract
(10)
Siponimod for patients with relapsing-remitting multiple sclerosis (BOLD): an adaptive, dose-ranging, randomised, phase 2 study.
Selmaj K, Li DKB, Hartung H-P, Hemmer B, Kappos L, Freedman MS, Stüve O, Rieckmann P, Montalban X, Ziemssen T, et al.
Lancet Neurol. 2013 Aug; 12(8):756-67. Epub 2013 Jun 11. PMID: 23764350. Abstract
(11)
Long-term Safety, Tolerability and Efficacy of BAF312 Given Orally in Patients With Relapsing-remitting Multiple Sclerosis
ClinicalTrials.gov, 18 Jan 2013
Accessed on 11 Aug 2013 from http://www.clinicaltrials.gov/ct2/show/NCT01185821.
Key Clinical Trials
Placebo-controlled Trials: 
Trial name: 
EXploring the efficacy and safety of siponimod in PAtients with SeconDary Progressive Multiple Sclerosis (EXPAND trial) (meeting abstracts, February 2013, November 2014)
(4)
Siponimod (BAF312) for the Treatment of Secondary Progressive Multiple Sclerosis: Design of the Phase 3 EXPAND Trial
Kappos L, Bar-Or A, Cree B, Fox R, Giovannoni G, Gold R, Vermersch P, Lam E, Pohlmann H, Zhang-Auberson L, et al., Neurology (Meeting Abstracts), 12 Feb 2013
Accessed on 11 Aug 2013 from http://www.neurology.org/cgi/content/meeting_abstract/80/1_MeetingAbstracts/P07.126.
(15)
Siponimod (BAF312) for the treatment of secondary progressive multiple sclerosis: Design of the phase 3 EXPAND trial.
Kappos L, Bar-Or A, Cree B, Fox R, Giovannoni G, Gold R, Vermersch P, Lam E, Pohlmann H, Wallström E
Mult Scler Relat Disord. 2014 Nov; 3(6):752. Epub 2014 Nov 21. PMID: 25891589. Abstract
Phase: 
Phase III trial
(4)
Siponimod (BAF312) for the Treatment of Secondary Progressive Multiple Sclerosis: Design of the Phase 3 EXPAND Trial
Kappos L, Bar-Or A, Cree B, Fox R, Giovannoni G, Gold R, Vermersch P, Lam E, Pohlmann H, Zhang-Auberson L, et al., Neurology (Meeting Abstracts), 12 Feb 2013
Accessed on 11 Aug 2013 from http://www.neurology.org/cgi/content/meeting_abstract/80/1_MeetingAbstracts/P07.126.
(15)
Siponimod (BAF312) for the treatment of secondary progressive multiple sclerosis: Design of the phase 3 EXPAND trial.
Kappos L, Bar-Or A, Cree B, Fox R, Giovannoni G, Gold R, Vermersch P, Lam E, Pohlmann H, Wallström E
Mult Scler Relat Disord. 2014 Nov; 3(6):752. Epub 2014 Nov 21. PMID: 25891589. Abstract
Study Design: 
Industry-sponsored, multicenter, randomized, double-blind, parallel-group, placebo-controlled variable treatment duration study to examine the safety, tolerability, and efficacy of siponimod (oral dose of 2 mg, given daily after an initial 6-day dose titration (0.25, 0.25, 0.5, 0.75, 1.25, and 2 mg) in delaying the time to 3-month confirmed disability progression (primary objective)
(4)
Siponimod (BAF312) for the Treatment of Secondary Progressive Multiple Sclerosis: Design of the Phase 3 EXPAND Trial
Kappos L, Bar-Or A, Cree B, Fox R, Giovannoni G, Gold R, Vermersch P, Lam E, Pohlmann H, Zhang-Auberson L, et al., Neurology (Meeting Abstracts), 12 Feb 2013
Accessed on 11 Aug 2013 from http://www.neurology.org/cgi/content/meeting_abstract/80/1_MeetingAbstracts/P07.126.
(15)
Siponimod (BAF312) for the treatment of secondary progressive multiple sclerosis: Design of the phase 3 EXPAND trial.
Kappos L, Bar-Or A, Cree B, Fox R, Giovannoni G, Gold R, Vermersch P, Lam E, Pohlmann H, Wallström E
Mult Scler Relat Disord. 2014 Nov; 3(6):752. Epub 2014 Nov 21. PMID: 25891589. Abstract
Disease Stage: 
SPMS
(4)
Siponimod (BAF312) for the Treatment of Secondary Progressive Multiple Sclerosis: Design of the Phase 3 EXPAND Trial
Kappos L, Bar-Or A, Cree B, Fox R, Giovannoni G, Gold R, Vermersch P, Lam E, Pohlmann H, Zhang-Auberson L, et al., Neurology (Meeting Abstracts), 12 Feb 2013
Accessed on 11 Aug 2013 from http://www.neurology.org/cgi/content/meeting_abstract/80/1_MeetingAbstracts/P07.126.
(15)
Siponimod (BAF312) for the treatment of secondary progressive multiple sclerosis: Design of the phase 3 EXPAND trial.
Kappos L, Bar-Or A, Cree B, Fox R, Giovannoni G, Gold R, Vermersch P, Lam E, Pohlmann H, Wallström E
Mult Scler Relat Disord. 2014 Nov; 3(6):752. Epub 2014 Nov 21. PMID: 25891589. Abstract
Enrollment/Number of Patients: 
1530 (estimated)
(4)
Siponimod (BAF312) for the Treatment of Secondary Progressive Multiple Sclerosis: Design of the Phase 3 EXPAND Trial
Kappos L, Bar-Or A, Cree B, Fox R, Giovannoni G, Gold R, Vermersch P, Lam E, Pohlmann H, Zhang-Auberson L, et al., Neurology (Meeting Abstracts), 12 Feb 2013
Accessed on 11 Aug 2013 from http://www.neurology.org/cgi/content/meeting_abstract/80/1_MeetingAbstracts/P07.126.
(15)
Siponimod (BAF312) for the treatment of secondary progressive multiple sclerosis: Design of the phase 3 EXPAND trial.
Kappos L, Bar-Or A, Cree B, Fox R, Giovannoni G, Gold R, Vermersch P, Lam E, Pohlmann H, Wallström E
Mult Scler Relat Disord. 2014 Nov; 3(6):752. Epub 2014 Nov 21. PMID: 25891589. Abstract
Duration: 
23 to 42 months (anticipated)
(4)
Siponimod (BAF312) for the Treatment of Secondary Progressive Multiple Sclerosis: Design of the Phase 3 EXPAND Trial
Kappos L, Bar-Or A, Cree B, Fox R, Giovannoni G, Gold R, Vermersch P, Lam E, Pohlmann H, Zhang-Auberson L, et al., Neurology (Meeting Abstracts), 12 Feb 2013
Accessed on 11 Aug 2013 from http://www.neurology.org/cgi/content/meeting_abstract/80/1_MeetingAbstracts/P07.126.
(15)
Siponimod (BAF312) for the treatment of secondary progressive multiple sclerosis: Design of the phase 3 EXPAND trial.
Kappos L, Bar-Or A, Cree B, Fox R, Giovannoni G, Gold R, Vermersch P, Lam E, Pohlmann H, Wallström E
Mult Scler Relat Disord. 2014 Nov; 3(6):752. Epub 2014 Nov 21. PMID: 25891589. Abstract
Status/Outcome: 
Recruiting participants as of July, 2013
(3)
Exploring the Efficacy and Safety of Siponimod in Patients With Secondary Progressive Multiple Sclerosis (EXPAND)
ClinicalTrials.gov, 29 Jul 2013
Accessed on 11 Aug 2013 from http://www.clinicaltrials.gov/ct2/show/NCT01665144.
Trial name: 
Selmaj et al., Lancet Neurol., August 2013 trial (BOLD trial)
(10)
Siponimod for patients with relapsing-remitting multiple sclerosis (BOLD): an adaptive, dose-ranging, randomised, phase 2 study.
Selmaj K, Li DKB, Hartung H-P, Hemmer B, Kappos L, Freedman MS, Stüve O, Rieckmann P, Montalban X, Ziemssen T, et al.
Lancet Neurol. 2013 Aug; 12(8):756-67. Epub 2013 Jun 11. PMID: 23764350. Abstract
Phase: 
Phase II trial
(10)
Siponimod for patients with relapsing-remitting multiple sclerosis (BOLD): an adaptive, dose-ranging, randomised, phase 2 study.
Selmaj K, Li DKB, Hartung H-P, Hemmer B, Kappos L, Freedman MS, Stüve O, Rieckmann P, Montalban X, Ziemssen T, et al.
Lancet Neurol. 2013 Aug; 12(8):756-67. Epub 2013 Jun 11. PMID: 23764350. Abstract
Study Design: 
Industry-sponsored, multicenter, randomized, double-blind, placebo-controlled, adaptive, dose-ranging trial to examine the dose-response relation of siponimod [oral dose of 10 mg, 2 mg, 0.5 mg, or placebo daily for 6 months (cohort 1) or 1.25 mg, 0.25 mg, or placebo daily for 3 months (cohort 2)] with MRI measures, with the primary endpoint the percentage reduction in the number of active lesions at 3 months
(10)
Siponimod for patients with relapsing-remitting multiple sclerosis (BOLD): an adaptive, dose-ranging, randomised, phase 2 study.
Selmaj K, Li DKB, Hartung H-P, Hemmer B, Kappos L, Freedman MS, Stüve O, Rieckmann P, Montalban X, Ziemssen T, et al.
Lancet Neurol. 2013 Aug; 12(8):756-67. Epub 2013 Jun 11. PMID: 23764350. Abstract
Disease Stage: 
RRMS
(10)
Siponimod for patients with relapsing-remitting multiple sclerosis (BOLD): an adaptive, dose-ranging, randomised, phase 2 study.
Selmaj K, Li DKB, Hartung H-P, Hemmer B, Kappos L, Freedman MS, Stüve O, Rieckmann P, Montalban X, Ziemssen T, et al.
Lancet Neurol. 2013 Aug; 12(8):756-67. Epub 2013 Jun 11. PMID: 23764350. Abstract
Enrollment/Number of Patients: 
297
(10)
Siponimod for patients with relapsing-remitting multiple sclerosis (BOLD): an adaptive, dose-ranging, randomised, phase 2 study.
Selmaj K, Li DKB, Hartung H-P, Hemmer B, Kappos L, Freedman MS, Stüve O, Rieckmann P, Montalban X, Ziemssen T, et al.
Lancet Neurol. 2013 Aug; 12(8):756-67. Epub 2013 Jun 11. PMID: 23764350. Abstract
Duration: 
6 months
(10)
Siponimod for patients with relapsing-remitting multiple sclerosis (BOLD): an adaptive, dose-ranging, randomised, phase 2 study.
Selmaj K, Li DKB, Hartung H-P, Hemmer B, Kappos L, Freedman MS, Stüve O, Rieckmann P, Montalban X, Ziemssen T, et al.
Lancet Neurol. 2013 Aug; 12(8):756-67. Epub 2013 Jun 11. PMID: 23764350. Abstract
Status/Outcome: 
A dose-response relation was found for all doses of siponimod, with reductions in combined unique active lesions at 3 months ranging from 35% (0.25 mg dose) to 82% (10 mg dose)
(10)
Siponimod for patients with relapsing-remitting multiple sclerosis (BOLD): an adaptive, dose-ranging, randomised, phase 2 study.
Selmaj K, Li DKB, Hartung H-P, Hemmer B, Kappos L, Freedman MS, Stüve O, Rieckmann P, Montalban X, Ziemssen T, et al.
Lancet Neurol. 2013 Aug; 12(8):756-67. Epub 2013 Jun 11. PMID: 23764350. Abstract
Trial name: 
Legangneux et al., Br. J. Clin. Pharmacol., March 2013 trial
(9)
Dose titration of BAF312 attenuates the initial heart rate reducing effect in healthy subjects.
Legangneux E, Gardin A, Johns D
Br J Clin Pharmacol. 2013 Mar; 75(3):831-41. PMID: 22845008. Abstract
Phase: 
Phase I trial
(9)
Dose titration of BAF312 attenuates the initial heart rate reducing effect in healthy subjects.
Legangneux E, Gardin A, Johns D
Br J Clin Pharmacol. 2013 Mar; 75(3):831-41. PMID: 22845008. Abstract
Study Design: 
Industry-sponsored, randomized, placebo-controlled study to determine if dose titration of siponimod reduces the transient decrease in heart rate that has been observed after an initial dose; the effects of two dose titration regimens (0.25 to 10 mg over 9 to 10 days) were compared with no titration (10 mg starting dose) or placebo
(9)
Dose titration of BAF312 attenuates the initial heart rate reducing effect in healthy subjects.
Legangneux E, Gardin A, Johns D
Br J Clin Pharmacol. 2013 Mar; 75(3):831-41. PMID: 22845008. Abstract
Disease Stage: 
Healthy individuals
(9)
Dose titration of BAF312 attenuates the initial heart rate reducing effect in healthy subjects.
Legangneux E, Gardin A, Johns D
Br J Clin Pharmacol. 2013 Mar; 75(3):831-41. PMID: 22845008. Abstract
Enrollment/Number of Patients: 
56
(9)
Dose titration of BAF312 attenuates the initial heart rate reducing effect in healthy subjects.
Legangneux E, Gardin A, Johns D
Br J Clin Pharmacol. 2013 Mar; 75(3):831-41. PMID: 22845008. Abstract
Duration: 
12 days
(9)
Dose titration of BAF312 attenuates the initial heart rate reducing effect in healthy subjects.
Legangneux E, Gardin A, Johns D
Br J Clin Pharmacol. 2013 Mar; 75(3):831-41. PMID: 22845008. Abstract
Status/Outcome: 
Titration regimens attenuated the drug-associated effects on heart rate, such that more favorable outcomes were observed in the titration groups on each day of the study versus the non-titration group day 1; in the titration groups, minor decreases in heart rate occurred on days 3 to 7 (as compared with the placebo group) and no decreases occurred on day 1; heart rates were similar in the placebo and titration groups on days 9 to 12
(9)
Dose titration of BAF312 attenuates the initial heart rate reducing effect in healthy subjects.
Legangneux E, Gardin A, Johns D
Br J Clin Pharmacol. 2013 Mar; 75(3):831-41. PMID: 22845008. Abstract
Trial name: 
Gergely et al., Br. J. Pharmacol., November 2012 trial
(1)
The selective sphingosine 1-phosphate receptor modulator BAF312 redirects lymphocyte distribution and has species-specific effects on heart rate.
Gergely P, Nuesslein-Hildesheim B, Guerini D, Brinkmann V, Traebert M, Bruns C, Pan S, Gray NS, Hinterding K, Cooke NG, et al.
Br J Pharmacol. 2012 Nov; 167(5):1035-47. PMID: 22646698. Abstract
Phase: 
Phase I trial
(1)
The selective sphingosine 1-phosphate receptor modulator BAF312 redirects lymphocyte distribution and has species-specific effects on heart rate.
Gergely P, Nuesslein-Hildesheim B, Guerini D, Brinkmann V, Traebert M, Bruns C, Pan S, Gray NS, Hinterding K, Cooke NG, et al.
Br J Pharmacol. 2012 Nov; 167(5):1035-47. PMID: 22646698. Abstract
Study Design: 
Industry-sponsored, randomized, parallel, double-blind, placebo-controlled trial to test the safety and tolerability of siponimod (a daily oral dose of 0.3, 1, 2.5, 10, or 20 mg) (primary objective), as well as its effects on lymphocyte counts and pharmacokinetic effects (secondary objectives)
(1)
The selective sphingosine 1-phosphate receptor modulator BAF312 redirects lymphocyte distribution and has species-specific effects on heart rate.
Gergely P, Nuesslein-Hildesheim B, Guerini D, Brinkmann V, Traebert M, Bruns C, Pan S, Gray NS, Hinterding K, Cooke NG, et al.
Br J Pharmacol. 2012 Nov; 167(5):1035-47. PMID: 22646698. Abstract
Disease Stage: 
Healthy individuals
(1)
The selective sphingosine 1-phosphate receptor modulator BAF312 redirects lymphocyte distribution and has species-specific effects on heart rate.
Gergely P, Nuesslein-Hildesheim B, Guerini D, Brinkmann V, Traebert M, Bruns C, Pan S, Gray NS, Hinterding K, Cooke NG, et al.
Br J Pharmacol. 2012 Nov; 167(5):1035-47. PMID: 22646698. Abstract
Enrollment/Number of Patients: 
48
(1)
The selective sphingosine 1-phosphate receptor modulator BAF312 redirects lymphocyte distribution and has species-specific effects on heart rate.
Gergely P, Nuesslein-Hildesheim B, Guerini D, Brinkmann V, Traebert M, Bruns C, Pan S, Gray NS, Hinterding K, Cooke NG, et al.
Br J Pharmacol. 2012 Nov; 167(5):1035-47. PMID: 22646698. Abstract
Duration: 
28 days of treatment; 49 days including follow-up period
(1)
The selective sphingosine 1-phosphate receptor modulator BAF312 redirects lymphocyte distribution and has species-specific effects on heart rate.
Gergely P, Nuesslein-Hildesheim B, Guerini D, Brinkmann V, Traebert M, Bruns C, Pan S, Gray NS, Hinterding K, Cooke NG, et al.
Br J Pharmacol. 2012 Nov; 167(5):1035-47. PMID: 22646698. Abstract
Status/Outcome: 
Drug was well tolerated; it was associated with a decline in the peripheral absolute lymphocyte count (ALC) [with declines ranging from 32.8% (0.3 mg dose) to 76.1% (20 mg dose)], with the greatest reduction occurring 4 to 6 hours after the dose; the drug affected leukocyte subsets differently, such that monocytes were largely unaffected and B and T cells strongly affected (with a greater effect on CD4+ T cells versus CD8+ T cells); the ALC returned to normal levels within 7 days after treatment ended (for the 0.3 to 10 mg doses); drug caused a transient, dose-dependent reduction in mean ventricular heart rate after the initial dose, which did not occur on subsequent days; no signs of macular edema were observed
(1)
The selective sphingosine 1-phosphate receptor modulator BAF312 redirects lymphocyte distribution and has species-specific effects on heart rate.
Gergely P, Nuesslein-Hildesheim B, Guerini D, Brinkmann V, Traebert M, Bruns C, Pan S, Gray NS, Hinterding K, Cooke NG, et al.
Br J Pharmacol. 2012 Nov; 167(5):1035-47. PMID: 22646698. Abstract
Head-to-Head Trials: 
Other Trials: 
Trial name: 
Extension of a Phase II trial of BAF312 in RRMS (BOLD; publ November 2014)
(11)
Long-term Safety, Tolerability and Efficacy of BAF312 Given Orally in Patients With Relapsing-remitting Multiple Sclerosis
ClinicalTrials.gov, 18 Jan 2013
Accessed on 11 Aug 2013 from http://www.clinicaltrials.gov/ct2/show/NCT01185821.
(14)
Phase 2 BOLD extension study efficacy results for siponimod (BAF312) in patients with relapsing-remitting multiple sclerosis.
Stuve O, Hartung HP, Freedman M, Li D, Hemmer B, Kappos L, Rieckmann P, Montalban X, Ziemssen T, Selmaj K
Mult Scler Relat Disord. 2014 Nov; 3(6):754-5. Epub 2014 Nov 21. PMID: 25891595. Abstract
Phase: 
Extension of a Phase II trial
(11)
Long-term Safety, Tolerability and Efficacy of BAF312 Given Orally in Patients With Relapsing-remitting Multiple Sclerosis
ClinicalTrials.gov, 18 Jan 2013
Accessed on 11 Aug 2013 from http://www.clinicaltrials.gov/ct2/show/NCT01185821.
Study Design: 
Industry-sponsored, dose-blinded extension of a Phase II trial of siponimod in RRMS
(10)
Siponimod for patients with relapsing-remitting multiple sclerosis (BOLD): an adaptive, dose-ranging, randomised, phase 2 study.
Selmaj K, Li DKB, Hartung H-P, Hemmer B, Kappos L, Freedman MS, Stüve O, Rieckmann P, Montalban X, Ziemssen T, et al.
Lancet Neurol. 2013 Aug; 12(8):756-67. Epub 2013 Jun 11. PMID: 23764350. Abstract
 to provide information about long-term safety and tolerability, with a focus on cardiovascular events, macular edema, viral infections, and dermatological issues (primary outcome measure) and efficacy (secondary outcome measures)
(11)
Long-term Safety, Tolerability and Efficacy of BAF312 Given Orally in Patients With Relapsing-remitting Multiple Sclerosis
ClinicalTrials.gov, 18 Jan 2013
Accessed on 11 Aug 2013 from http://www.clinicaltrials.gov/ct2/show/NCT01185821.
; participants continued on doses from the original trial or were re-allocated to siponimod at a dose of 10 mg, 2 mg, 1.25 mg, 0.5 mg, or 0.25 mg
(14)
Phase 2 BOLD extension study efficacy results for siponimod (BAF312) in patients with relapsing-remitting multiple sclerosis.
Stuve O, Hartung HP, Freedman M, Li D, Hemmer B, Kappos L, Rieckmann P, Montalban X, Ziemssen T, Selmaj K
Mult Scler Relat Disord. 2014 Nov; 3(6):754-5. Epub 2014 Nov 21. PMID: 25891595. Abstract
Disease Stage: 
RRMS
(11)
Long-term Safety, Tolerability and Efficacy of BAF312 Given Orally in Patients With Relapsing-remitting Multiple Sclerosis
ClinicalTrials.gov, 18 Jan 2013
Accessed on 11 Aug 2013 from http://www.clinicaltrials.gov/ct2/show/NCT01185821.
Enrollment/Number of Patients: 
184
(14)
Phase 2 BOLD extension study efficacy results for siponimod (BAF312) in patients with relapsing-remitting multiple sclerosis.
Stuve O, Hartung HP, Freedman M, Li D, Hemmer B, Kappos L, Rieckmann P, Montalban X, Ziemssen T, Selmaj K
Mult Scler Relat Disord. 2014 Nov; 3(6):754-5. Epub 2014 Nov 21. PMID: 25891595. Abstract
Duration: 
12 months
(14)
Phase 2 BOLD extension study efficacy results for siponimod (BAF312) in patients with relapsing-remitting multiple sclerosis.
Stuve O, Hartung HP, Freedman M, Li D, Hemmer B, Kappos L, Rieckmann P, Montalban X, Ziemssen T, Selmaj K
Mult Scler Relat Disord. 2014 Nov; 3(6):754-5. Epub 2014 Nov 21. PMID: 25891595. Abstract
Status/Outcome: 
Lesion activity and annual relapse rates (ARRs) stayed low, especially for the 10, 2, and 1.25 mg dose groups (with ARRs of 0.27, 0.18, and 0.13, respectively)
(14)
Phase 2 BOLD extension study efficacy results for siponimod (BAF312) in patients with relapsing-remitting multiple sclerosis.
Stuve O, Hartung HP, Freedman M, Li D, Hemmer B, Kappos L, Rieckmann P, Montalban X, Ziemssen T, Selmaj K
Mult Scler Relat Disord. 2014 Nov; 3(6):754-5. Epub 2014 Nov 21. PMID: 25891595. Abstract
References
ChemIDplus Advanced
United States National Library of Medicine
Accessed on 29 Jul 2013 from http://chem.sis.nlm.nih.gov/chemidplus/chemidheavy.jsp.

Note: Compound name must be entered under "Substance Identification" and then "Names and Synonyms" selected to view synonyms.

DOI: 
doi/10.7493/msdf.10.7176.1