Page last updated: 2024-11-12

ponesimod

Description Research Excerpts Clinical Trials Roles Classes Pathways Study Profile Bioassays Related Drugs Related Conditions Protein Interactions Research Growth Market Indicators

Description

ponesimod: structure in first source [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID Source	ID
PubMed CID	11363176
CHEMBL ID	1096146
SCHEMBL ID	15477937
SCHEMBL ID	15477934
MeSH ID	M0547425

Synonyms (47)

Synonym
act-128800
ponesimod
CHEMBL1096146 ,
bdbm50316768
(z,z)-5-[3-chloro-4-((2s)-2,3-dihydroxy-propoxy)-benzylidene]-2-propylimino-3-otolyl-thiazolidin-4-one
enb-0040
5-(3-chloro-4-(2,3-dihydroxy-propoxy)benzylidene)-2-propylimino-3-o-tolyl-thiazolidin-4-one
act128800
act 128800
5g7akv2mkp ,
(2z,5z)-5-(3-chloro-4-((2r)-2,3-dihydroxypropoxy)phenylmethylidene)-3-(2-methylphenyl)-2-(propylimino)-1,3-thiazolidin-4-one
ponesimod [usan:inn]
854107-55-4
unii-5g7akv2mkp
ponvory
S8241
AKOS022180266
ponesimod [inn]
5-(3-chloro-4-(((2r)-2,3-dihydroxypropyl)oxy)benz-(z)-ylidene)-2-((z)-propylimino)-3-(o-tolyl)thiazolidin-4-one
ponesimod [usan]
(2z,5z)-5-(3-chloro-4-((2r)-2,3-dihydroxypropoxy)benzylidene)-3-(2-methylphenyl)-2-(propylimino)-1,3-thiazolidin-4-one
ponesimod [who-dd]
ponesimod [orange book]
4-thiazolidinone, 5-((3-chloro-4-((2r)-2,3-dihydroxypropoxy)phenyl)methylene)-3-(2-methylphenyl)-2-(propylimino)-, (2z,5z)-
DTXSID50234631 ,
SCHEMBL15477937
SCHEMBL15477934
(5z)-5-[[3-chloro-4-[(2r)-2,3-dihydroxypropoxy]phenyl]methylidene]-3-(2-methylphenyl)-2-propylimino-1,3-thiazolidin-4-one
gtpl9320
compound 8bo [pmid:20446681]
HY-10569
AC-30921
4-thiazolidinone, 5-[[3-chloro-4-[(2r)-2,3-dihydroxypropoxy]phenyl]methylene]-3-(2-methylphenyl)-2-(propylimino)-, (2z,5z)-
mfcd18207776
DB12016
ponesimod (act-128800)
ponesimod,act-128800
EX-A1417
(2z,5z)-5-(3-chloro-4-((r)-2,3-dihydroxypropoxy)benzylidene)-2-(propylimino)-3-(o-tolyl)thiazolidin-4-one
AS-35140
ponesimod (usan/inn)
D11215
AMY23424
CCG-269345
(z)-5-((z)-3-chloro-4-((r)-2,3-dihydroxypropoxy)benzylidene)-2-(propylimino)-3-(o-tolyl)thiazolidin-4-one
AT27979
BP175283

Research Excerpts

Overview

Ponesimod is an orally administered second-generation sphingosine 1-phospate (S1-P) receptor modulator classified as a disease modifying treatment (DMT) for MS.

Excerpt	Reference	Relevance
"Ponesimod (ACT-128800) is a directly bioavailable, rapidly reversible sphingosine-1-phosphate (S1P) receptor modulator, highly selective for the subtype 1 (S1P₁ receptor). "	( Ponesimod to treat multiple sclerosis. Ianniello, A; Pozzilli, C, 2021)	3.51
"Ponesimod is a sphingosine 1-phosphate (S1P) receptor (S1PR) modulator that was recently approved for treating relapsing forms of multiple sclerosis (MS). "	( Ponesimod inhibits astrocyte-mediated neuroinflammation and protects against cingulum demyelination via S1P Chun, J; Jonnalagadda, D; Kihara, Y; Ngo, T; Palmer, C; Ray, M; Rivera, R; Zhu, Y, 2022)	3.61
"Ponesimod is an orally administered second-generation sphingosine 1-phospate (S1-P) receptor modulator classified as a disease modifying treatment (DMT) for MS. "	( Ponesimod: An Oral Second-Generation Selective Sphingosine 1-Phosphate Receptor Modulator for the Treatment of Multiple Sclerosis. Alnaif, A; D'Souza, MS; Oiler, I, 2023)	3.8
"Ponesimod is a sphingosphine-1-phosphate receptor modulator being developed for the treatment of multiple sclerosis. "	( An Exposure-Response Analysis of the Clinical Efficacy of Ponesimod in a Randomized Phase II Study in Patients with Multiple Sclerosis. Burcklen, M; Gisleskog, PO; Pérez-Ruixo, JJ; Poggesi, I; Scherz, T; Valenzuela, B, 2021)	2.31
"Ponesimod (PONVORY™) is an orally administered selective sphingosine-1-phosphate (S1P) receptor 1 (S1P"	( Ponesimod: First Approval. Markham, A, 2021)	3.51
"Oral ponesimod is a new therapy for the treatment of moderate-to-severe plaque psoriasis. "	( Oral ponesimod for psoriasis compared to other investigational therapies. Reddy, SP; Wu, JJ, 2016)	1.46
"Ponesimod is an orally active selective sphingosine-1-phosphate receptor 1 modulator under investigation for the treatment of multiple sclerosis. "	( Effect of ponesimod, a selective S1P1 receptor modulator, on the QT interval in healthy individuals. Brossard, P; Darpo, B; Dingemanse, J; Hoch, M; Stoltz, R; Zhou, M, 2015)	2.26
"Ponesimod is a selective S1P1 receptor modulator, and induces dose-dependent reduction of circulating lymphocytes upon oral dosing. "	( Three different up-titration regimens of ponesimod, an S1P1 receptor modulator, in healthy subjects. Brossard, P; D'Ambrosio, D; Dingemanse, J; Ipek, M; Scherz, MW, 2015)	2.13
"Ponesimod is a potent selective sphingosine-1-phosphate receptor 1 (S1P1) modulator, which leads to a reduction in circulating lymphocytes, reflecting their sequestration within lymphoid organs. "	( Biocomparison of Three Formulations of the S1P1 Receptor Modulator Ponesimod in Healthy Subjects. D'Ambrosio, D; Dingemanse, J; Hoch, M; Juif, PE, 2015)	2.1
"Ponesimod is a selective, orally active sphingosine-1-phosphate receptor 1 modulator currently undergoing clinical evaluation for the treatment of multiple sclerosis (MS) in phase III clinical trials. "	( Impact of Demographics, Organ Impairment, Disease, Formulation, and Food on the Pharmacokinetics of the Selective S1P Dingemanse, J; Krause, A; Lehr, T; Lott, D, 2017)	1.9

Actions

Excerpt	Reference	Relevance
"Ponesimod did not inhibit the differentiation of autoreactive T cells as assessed by adoptive transfer of lymphocytes from treated disease-free NOD mice."	( Therapeutic use of a selective S1P1 receptor modulator ponesimod in autoimmune diabetes. Bach, JF; Chatenoud, L; Clozel, M; Kuhn, C; Piali, L; Sauvaget, V; Steiner, B; Valette, F; You, S, 2013)	1.36

Treatment

Excerpt	Reference	Relevance
"Ponesimod treatment ameliorated EAE and alleviated inflammatory infiltration."	( Ponesimod modulates the Th1/Th17/Treg cell balance and ameliorates disease in experimental autoimmune encephalomyelitis. Gao, M; Guo, L; Hou, H; Miao, J; Song, X; Sun, Y, 2021)	2.79

Toxicity

Excerpt	Reference	Relevance
" Sixteen adverse events (AEs) were reported, 12 of them of mild intensity."	( Effect of Hepatic or Renal Impairment on the Pharmacokinetics, Safety, and Tolerability of Ponesimod, a Selective S1P1 Receptor Modulator. Dingemanse, J; Guérard, N; Hoch, M; Zwingelstein, C, 2016)	0.65
" Outcomes included annualized relapse rate (ARR) and percentage change from baseline in brain volume loss (BVL) as well as rates of any treatment-emergent adverse events (TEAEs), serious adverse events (AEs), AEs leading to discontinuation, and other safety outcomes."	( Comparative efficacy and safety of ozanimod and ponesimod for relapsing multiple sclerosis: A matching-adjusted indirect comparison. Gomez-Lievano, A; Gupte-Singh, K; Liu, J; Patterson-Lomba, O; Pham, T; Swallow, E; Tencer, T; Yin, L, 2023)	1.17

Pharmacokinetics

Ponesimod multiple-dose pharmacokinetics were slightly more than dose-proportional and characterized by a time to maximum concentration and an elimination half-life varying from 2.5 to 2.7 hours. Ponesimmod population PK was characterized by an open two-compartment disposition model with a terminal half- life of 33 h.

Excerpt	Reference	Relevance
"0 h, and ponesimod was eliminated with a mean half-life varying between 21."	( Pharmacokinetics and pharmacodynamics of ponesimod, a selective S1P1 receptor modulator, in the first-in-human study. Brossard, P; Derendorf, H; Dingemanse, J; Halabi, A; Maatouk, H; Xu, J, 2013)	1.07
"The aim of this study was to evaluate the relative pharmacokinetic (PK) and pharmacodynamic (PD) properties of a single dose of ponesimod, an oral and selective sphingosine-1-phosphate receptor 1 (S1P1) modulator, in Japanese and Caucasian healthy subjects and explore the effects of sex on PK."	( Effects of ethnicity and sex on the pharmacokinetics and pharmacodynamics of the selective sphingosine-1-phosphate receptor 1 modulator ponesimod: a clinical study in Japanese and Caucasian subjects. Brossard, P; Dingemanse, J; Hoch, M; Reyes, M, 2014)	0.81
" Cmax and tmax values of ponesimod were comparable across all groups in both studies."	( Effect of Hepatic or Renal Impairment on the Pharmacokinetics, Safety, and Tolerability of Ponesimod, a Selective S1P1 Receptor Modulator. Dingemanse, J; Guérard, N; Hoch, M; Zwingelstein, C, 2016)	0.96
" Based on clinical data including studies in renally and hepatically impaired subjects, a population pharmacokinetic (PK) model was developed to characterize the PK of ponesimod and its primary metabolites and to qualify and quantify the influence of organ impairment on the concentration-time profiles of these compounds."	( Population pharmacokinetics of ponesimod and its primary metabolites in healthy and organ-impaired subjects. Dingemanse, J; Krause, A; Lehr, T; Lott, D, 2016)	0.92
"A population pharmacokinetic (PK) analysis was performed based on pooled data from 13 clinical studies."	( Impact of Demographics, Organ Impairment, Disease, Formulation, and Food on the Pharmacokinetics of the Selective S1P Dingemanse, J; Krause, A; Lehr, T; Lott, D, 2017)	0.46
" A previous pharmacokinetic (PK) and pharmacodynamic model developed in healthy participants was updated using data from phase II and III trials conducted in patients with MS."	( Pharmacokinetic-Pharmacodynamic Modeling of the Ponesimod Effect on Heart Rate in Patients With Multiple Sclerosis. Luyckx, N; Pérez-Ruixo, JJ; Poggesi, I; Vaclavkova, A; Valenzuela, B, 2023)	1.17

Bioavailability

Excerpt	Reference	Relevance
"The aim of this study was to compare the relative bioavailability of two polymorphic forms of ponesimod in capsules (Form A versus Form C; Study 1) and the relative bioavailability of a capsule formulation and a tablet formulation (both polymorphic Form C; Study 2)."	( Biocomparison of Three Formulations of the S1P1 Receptor Modulator Ponesimod in Healthy Subjects. D'Ambrosio, D; Dingemanse, J; Hoch, M; Juif, PE, 2015)	0.87

Dosage Studied

To evaluate the dose-response relationship of 10, 20, and 40 mg ponesimod. Sex, age, T1 Gd+ lesions at baseline, and Expanded Disability Status Score at baseline were not found to be important. An uptitration dosing scheme is to be preferred in cl.

Excerpt	Relevance	Reference
" Pharmacokinetic investigation of 8bo in beagle dogs suggests that the compound is suitable for once daily dosing in humans."	( 2-imino-thiazolidin-4-one derivatives as potent, orally active S1P1 receptor agonists. Abele, S; Binkert, C; Bolli, MH; Bravo, R; Buchmann, S; Bur, D; Gatfield, J; Hess, P; Kohl, C; Mangold, C; Mathys, B; Menyhart, K; Müller, C; Nayler, O; Scherz, M; Schmidt, G; Sippel, V; Steiner, B; Strasser, D; Treiber, A; Weller, T, 2010)	0.36
" Repeated oral dosing of 1 or 3 mg/kg ponesimod resulted in rapid desensitization, so that the second dose had no or a clearly reduced effect on ECG variables as compared with the first dose."	( Desensitization by progressive up-titration prevents first-dose effects on the heart: guinea pig study with ponesimod, a selective S1P1 receptor modulator. Clozel, M; Delahaye, S; Gatfield, J; Hess, P; Nayler, O; Rey, M; Steiner, B, 2013)	0.87
" The availability of a variety of doses, dosing regimens, and treatment durations permitted estimation of the pharmacokinetics characterized by an absorption lag time followed by a sequential zero/first-order absorption and two compartments with first-order elimination."	( Population pharmacokinetics and pharmacodynamics of ponesimod, a selective S1P1 receptor modulator. Brossard, P; D'Ambrosio, D; Dingemanse, J; Krause, A, 2014)	0.65
" An uptitration dosing scheme is to be preferred in clinical studies in patients in order to limit effects of ponesimod on heart rate and atrioventricular (AV) conduction."	( Clinical pharmacology of ponesimod, a selective S1P₁ receptor modulator, after uptitration to supratherapeutic doses in healthy subjects. Brossard, P; D'Ambrosio, D; Dingemanse, J; Hoch, M; Wilbraham, D, 2014)	0.92
" dosing (2."	( Three different up-titration regimens of ponesimod, an S1P1 receptor modulator, in healthy subjects. Brossard, P; D'Ambrosio, D; Dingemanse, J; Ipek, M; Scherz, MW, 2015)	0.68
"In order to study the role of S1PRs in inflammatory skin disease, S1PR modulators are dosed orally and topically in animal models of disease."	( Discovery of Soft-Drug Topical Tool Modulators of Sphingosine-1-phosphate Receptor 1 (S1PR1). Bell, M; Ellis, L; Epemolu, O; Ferguson, L; Fletcher, D; Foley, D; Katz, E; McLean, WHI; Naylor, C; Osuna-Cabello, M; Pinto, E; Read, KD; Riley, J; Robinson, C; Scullion, P; Shishikura, Y; Wood, G; Woodland, A; Wyatt, P, 2019)	0.51
" Sex, age, T1 Gd+ lesions at baseline, and Expanded Disability Status Score at baseline were not found to be importantly associated with the magnitude of ponesimod effect, and consequently, there is no indication from these analyses that dosage adjustments based on the explored covariates are warranted."	( An Exposure-Response Analysis of the Clinical Efficacy of Ponesimod in a Randomized Phase II Study in Patients with Multiple Sclerosis. Burcklen, M; Gisleskog, PO; Pérez-Ruixo, JJ; Poggesi, I; Scherz, T; Valenzuela, B, 2021)	1.06
"To evaluate the dose-response relationship of 10, 20, and 40 mg ponesimod and long-term efficacy and safety of ponesimod 20 mg using an analysis of combined data from the phase 2 Core and Extension studies in patients with relapsing-remitting multiple sclerosis (RRMS)."	( Long-term Treatment With Ponesimod in Relapsing-Remitting Multiple Sclerosis: Results From Randomized Phase 2b Core and Extension Studies. Burcklen, M; Freedman, MS; Havrdova, EK; Hennessy, B; Larbalestier, A; Lemle, A; Olsson, T; Pozzilli, C; Sidorenko, T; Vaclavkova, A, 2022)	1.26
" No significant baseline covariates affected the ponesimod effects and, consequently, dosage adjustments are not warranted by these analyses."	( An exposure-response analysis of ponesimod clinical efficacy in a randomized phase III study in patients with relapsing multiple sclerosis. Burcklen, M; Kracker, H; Olsson Gisleskog, P; Pérez-Ruixo, JJ; Poggesi, I; Sidorenko, T; Valenzuela, B, 2022)	1.26
" After repeated dosing at 20 mg, tolerance was maintained > 60% of the steady-state tolerance for up to 4 days after the last dose."	( Pharmacokinetic-Pharmacodynamic Modeling of the Ponesimod Effect on Heart Rate in Patients With Multiple Sclerosis. Luyckx, N; Pérez-Ruixo, JJ; Poggesi, I; Vaclavkova, A; Valenzuela, B, 2023)	1.17
" Furthermore, a dose-dependent reduction of peripheral lymphocyte counts that is sustained with continued daily oral dosing of ponesimod and is rapidly (4-7 days) reversible upon drug discontinuation has been characterized with an indirect response model."	( Clinical Pharmacokinetics of Ponesimod, a Selective S1P1 Receptor Modulator, in the Treatment of Multiple Sclerosis. Kruger, TM; Ouwerkerk-Mahadevan, S; Ruixo, JJP; Thompson, CD; Valenzuela, B, 2023)	1.41

[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Protein Targets (2)

Inhibition Measurements

Protein	Taxonomy	Measurement	Average	Min (ref.)	Avg (ref.)	Max (ref.)	Bioassay(s)
Sphingosine 1-phosphate receptor 1	Homo sapiens (human)	IC50 (µMol)	0.0126	0.0000	0.0855	0.8400	AID1420300
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Activation Measurements

Protein	Taxonomy	Measurement	Average	Min (ref.)	Avg (ref.)	Max (ref.)	Bioassay(s)
Sphingosine 1-phosphate receptor 1	Homo sapiens (human)	EC50 (µMol)	0.0097	0.0000	0.1759	7.8700	AID481618
Sphingosine 1-phosphate receptor 3	Homo sapiens (human)	EC50 (µMol)	0.1090	0.0001	0.3092	5.0000	AID481619
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (37)

Process	via Protein(s)	Taxonomy
blood vessel maturation	Sphingosine 1-phosphate receptor 1	Homo sapiens (human)
cardiac muscle tissue growth involved in heart morphogenesis	Sphingosine 1-phosphate receptor 1	Homo sapiens (human)
sphingosine-1-phosphate receptor signaling pathway	Sphingosine 1-phosphate receptor 1	Homo sapiens (human)
chemotaxis	Sphingosine 1-phosphate receptor 1	Homo sapiens (human)
cell adhesion	Sphingosine 1-phosphate receptor 1	Homo sapiens (human)
G protein-coupled receptor signaling pathway	Sphingosine 1-phosphate receptor 1	Homo sapiens (human)
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	Sphingosine 1-phosphate receptor 1	Homo sapiens (human)
phospholipase C-activating G protein-coupled receptor signaling pathway	Sphingosine 1-phosphate receptor 1	Homo sapiens (human)
brain development	Sphingosine 1-phosphate receptor 1	Homo sapiens (human)
cell population proliferation	Sphingosine 1-phosphate receptor 1	Homo sapiens (human)
cell migration	Sphingosine 1-phosphate receptor 1	Homo sapiens (human)
transmission of nerve impulse	Sphingosine 1-phosphate receptor 1	Homo sapiens (human)
lamellipodium assembly	Sphingosine 1-phosphate receptor 1	Homo sapiens (human)
actin cytoskeleton organization	Sphingosine 1-phosphate receptor 1	Homo sapiens (human)
regulation of cell adhesion	Sphingosine 1-phosphate receptor 1	Homo sapiens (human)
neuron differentiation	Sphingosine 1-phosphate receptor 1	Homo sapiens (human)
positive regulation of cell migration	Sphingosine 1-phosphate receptor 1	Homo sapiens (human)
regulation of bone mineralization	Sphingosine 1-phosphate receptor 1	Homo sapiens (human)
leukocyte chemotaxis	Sphingosine 1-phosphate receptor 1	Homo sapiens (human)
regulation of bone resorption	Sphingosine 1-phosphate receptor 1	Homo sapiens (human)
endothelial cell differentiation	Sphingosine 1-phosphate receptor 1	Homo sapiens (human)
positive regulation of transcription by RNA polymerase II	Sphingosine 1-phosphate receptor 1	Homo sapiens (human)
positive regulation of smooth muscle cell proliferation	Sphingosine 1-phosphate receptor 1	Homo sapiens (human)
positive regulation of positive chemotaxis	Sphingosine 1-phosphate receptor 1	Homo sapiens (human)
negative regulation of stress fiber assembly	Sphingosine 1-phosphate receptor 1	Homo sapiens (human)
heart trabecula morphogenesis	Sphingosine 1-phosphate receptor 1	Homo sapiens (human)
T cell migration	Sphingosine 1-phosphate receptor 1	Homo sapiens (human)
angiogenesis	Sphingosine 1-phosphate receptor 1	Homo sapiens (human)
regulation of metabolic process	Sphingosine 1-phosphate receptor 1	Homo sapiens (human)
adenylate cyclase-activating G protein-coupled receptor signaling pathway	Sphingosine 1-phosphate receptor 1	Homo sapiens (human)
sphingosine-1-phosphate receptor signaling pathway	Sphingosine 1-phosphate receptor 3	Homo sapiens (human)
inflammatory response	Sphingosine 1-phosphate receptor 3	Homo sapiens (human)
G protein-coupled receptor signaling pathway	Sphingosine 1-phosphate receptor 3	Homo sapiens (human)
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	Sphingosine 1-phosphate receptor 3	Homo sapiens (human)
positive regulation of cytosolic calcium ion concentration	Sphingosine 1-phosphate receptor 3	Homo sapiens (human)
Notch signaling pathway	Sphingosine 1-phosphate receptor 3	Homo sapiens (human)
positive regulation of cell population proliferation	Sphingosine 1-phosphate receptor 3	Homo sapiens (human)
anatomical structure morphogenesis	Sphingosine 1-phosphate receptor 3	Homo sapiens (human)
regulation of interleukin-1 beta production	Sphingosine 1-phosphate receptor 3	Homo sapiens (human)
negative regulation of establishment of endothelial barrier	Sphingosine 1-phosphate receptor 3	Homo sapiens (human)
adenylate cyclase-activating G protein-coupled receptor signaling pathway	Sphingosine 1-phosphate receptor 3	Homo sapiens (human)
regulation of metabolic process	Sphingosine 1-phosphate receptor 3	Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (7)

Process	via Protein(s)	Taxonomy
G protein-coupled receptor binding	Sphingosine 1-phosphate receptor 1	Homo sapiens (human)
G protein-coupled receptor activity	Sphingosine 1-phosphate receptor 1	Homo sapiens (human)
protein binding	Sphingosine 1-phosphate receptor 1	Homo sapiens (human)
sphingosine-1-phosphate receptor activity	Sphingosine 1-phosphate receptor 1	Homo sapiens (human)
sphingolipid binding	Sphingosine 1-phosphate receptor 1	Homo sapiens (human)
integrin binding	Sphingosine 1-phosphate receptor 3	Homo sapiens (human)
protein binding	Sphingosine 1-phosphate receptor 3	Homo sapiens (human)
lipid binding	Sphingosine 1-phosphate receptor 3	Homo sapiens (human)
sphingosine-1-phosphate receptor activity	Sphingosine 1-phosphate receptor 3	Homo sapiens (human)
G protein-coupled receptor activity	Sphingosine 1-phosphate receptor 3	Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (7)

Process	via Protein(s)	Taxonomy
nucleoplasm	Sphingosine 1-phosphate receptor 1	Homo sapiens (human)
endosome	Sphingosine 1-phosphate receptor 1	Homo sapiens (human)
plasma membrane	Sphingosine 1-phosphate receptor 1	Homo sapiens (human)
external side of plasma membrane	Sphingosine 1-phosphate receptor 1	Homo sapiens (human)
intracellular membrane-bounded organelle	Sphingosine 1-phosphate receptor 1	Homo sapiens (human)
membrane raft	Sphingosine 1-phosphate receptor 1	Homo sapiens (human)
plasma membrane	Sphingosine 1-phosphate receptor 1	Homo sapiens (human)
cytoplasm	Sphingosine 1-phosphate receptor 1	Homo sapiens (human)
plasma membrane	Sphingosine 1-phosphate receptor 3	Homo sapiens (human)
cytoplasm	Sphingosine 1-phosphate receptor 3	Homo sapiens (human)
plasma membrane	Sphingosine 1-phosphate receptor 3	Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (18)

Assay ID	Title	Year	Journal	Article
AID1054249	Half life of the compound	2013	Bioorganic & medicinal chemistry letters, Dec-01, Volume: 23, Issue:23	Modulators of the Sphingosine 1-phosphate receptor 1.
AID1474286	Toxicity in human assessed as reduction in heart rate at 10 mg measured on day 1	2017	Journal of medicinal chemistry, 07-13, Volume: 60, Issue:13	Modulators of Sphingosine-1-phosphate Pathway Biology: Recent Advances of Sphingosine-1-phosphate Receptor 1 (S1P
AID1420307	Antiinflammatory activity in psoriasis patient assessed as incident of 75% reduction in psoriasis area and severity index score at 40 mg, po dosed daily during phase 2 study for 28 weeks	2018	Bioorganic & medicinal chemistry letters, 10-15, Volume: 28, Issue:19	Discovery of super soft-drug modulators of sphingosine-1-phosphate receptor 1.
AID1420300	Inhibition of S1PR1 (unknown origin) expressed in CHOK1 cells after 90 mins by beta-arresting recuitment assay	2018	Bioorganic & medicinal chemistry letters, 10-15, Volume: 28, Issue:19	Discovery of super soft-drug modulators of sphingosine-1-phosphate receptor 1.
AID481618	Agonist activity at human recombinant S1P1 receptor expressed in CHO cells by GTPgammaS binding assay	2010	Journal of medicinal chemistry, May-27, Volume: 53, Issue:10	2-imino-thiazolidin-4-one derivatives as potent, orally active S1P1 receptor agonists.
AID1696040	Stability of compound in DMSO assessed as decrease in purity incubated for 28 days	2019	ACS medicinal chemistry letters, Mar-14, Volume: 10, Issue:3	Discovery of Soft-Drug Topical Tool Modulators of Sphingosine-1-phosphate Receptor 1 (S1PR1).
AID481621	Immunomodulatory activity in normotensive Wistar rat assessed as change in circulating lymphocytes count at 10 mg/kg, po after 6 hrs relative to control	2010	Journal of medicinal chemistry, May-27, Volume: 53, Issue:10	2-imino-thiazolidin-4-one derivatives as potent, orally active S1P1 receptor agonists.
AID1420301	Chromatographic hydrophobicity index, log D of the compound by reverse-phase HPLC analysis	2018	Bioorganic & medicinal chemistry letters, 10-15, Volume: 28, Issue:19	Discovery of super soft-drug modulators of sphingosine-1-phosphate receptor 1.
AID481622	Immunomodulatory activity in normotensive Wistar rat assessed as change in circulating lymphocytes count at 10 mg/kg, po after 24 hrs relative to control	2010	Journal of medicinal chemistry, May-27, Volume: 53, Issue:10	2-imino-thiazolidin-4-one derivatives as potent, orally active S1P1 receptor agonists.
AID1420303	Half life in human plasma at 37 degC	2018	Bioorganic & medicinal chemistry letters, 10-15, Volume: 28, Issue:19	Discovery of super soft-drug modulators of sphingosine-1-phosphate receptor 1.
AID481620	Immunomodulatory activity in normotensive Wistar rat assessed as change in circulating lymphocytes count at 10 mg/kg, po after 3 hrs relative to control	2010	Journal of medicinal chemistry, May-27, Volume: 53, Issue:10	2-imino-thiazolidin-4-one derivatives as potent, orally active S1P1 receptor agonists.
AID1420302	Kinetic solubility of the compound by laser nephelometric analysis	2018	Bioorganic & medicinal chemistry letters, 10-15, Volume: 28, Issue:19	Discovery of super soft-drug modulators of sphingosine-1-phosphate receptor 1.
AID1696042	Metabolic stability in human skin S9 cells assessed as half life at 0.5 uM incubated for 180 mins by UPLC-MS/MS analysis	2019	ACS medicinal chemistry letters, Mar-14, Volume: 10, Issue:3	Discovery of Soft-Drug Topical Tool Modulators of Sphingosine-1-phosphate Receptor 1 (S1PR1).
AID481619	Agonist activity at human recombinant S1P3 receptor expressed in CHO cells by GTPgammaS binding assay	2010	Journal of medicinal chemistry, May-27, Volume: 53, Issue:10	2-imino-thiazolidin-4-one derivatives as potent, orally active S1P1 receptor agonists.
AID1346205	Human S1P3 receptor (Lysophospholipid (S1P) receptors)	2010	Journal of medicinal chemistry, May-27, Volume: 53, Issue:10	2-imino-thiazolidin-4-one derivatives as potent, orally active S1P1 receptor agonists.
AID1346162	Human S1P4 receptor (Lysophospholipid (S1P) receptors)	2010	Journal of medicinal chemistry, May-27, Volume: 53, Issue:10	2-imino-thiazolidin-4-one derivatives as potent, orally active S1P1 receptor agonists.
AID1346242	Human S1P5 receptor (Lysophospholipid (S1P) receptors)	2010	Journal of medicinal chemistry, May-27, Volume: 53, Issue:10	2-imino-thiazolidin-4-one derivatives as potent, orally active S1P1 receptor agonists.
AID1346170	Human S1P1 receptor (Lysophospholipid (S1P) receptors)	2010	Journal of medicinal chemistry, May-27, Volume: 53, Issue:10	2-imino-thiazolidin-4-one derivatives as potent, orally active S1P1 receptor agonists.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (62)

Timeframe	Studies, This Drug (%)	All Drugs %
pre-1990	0 (0.00)	18.7374
1990's	0 (0.00)	18.2507
2000's	0 (0.00)	29.6817
2010's	40 (64.52)	24.3611
2020's	22 (35.48)	2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 63.39

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be very strong demand-to-supply ratio for research on this compound.

Metric	This Compound (vs All)
Research Demand Index	63.39 (24.57)
Research Supply Index	4.41 (2.92)
Research Growth Index	6.91 (4.65)
Search Engine Demand Index	100.41 (26.88)
Search Engine Supply Index	2.00 (0.95)

This Compound (63.39)

All Compounds (24.57)

Study Types

Publication Type	This drug (%)	All Drugs (%)
Trials	19 (30.65%)	5.53%
Reviews	15 (24.19%)	6.00%
Case Studies	1 (1.61%)	4.05%
Observational	0 (0.00%)	0.25%
Other	27 (43.55%)	84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (19)

Trial Overview

Trial	Phase	Enrollment	Study Type	Start Date	Status
Multicenter, Randomized, Double-blind, Parallel-group, add-on, Superiority Study to Compare the Efficacy and Safety of Ponesimod to Placebo in Subjects With Active Relapsing Multiple Sclerosis Who Are Treated With Dimethyl Fumarate (Tecfidera®) [NCT02907177]	Phase 3	136 participants (Actual)	Interventional	2017-03-30	Terminated(stopped due to sponsor decision due to low recruitment)
A Randomized, Double-blind, Parallel-group, 2-period, Placebo-controlled, Phase 1 Study to Investigate the Effects on Heart Rate, Blood Pressure, and Pharmacokinetic Interactions of the Up-titration Regimen of Ponesimod in Healthy Adult Subjects Receiving [NCT03882255]	Phase 1	52 participants (Actual)	Interventional	2019-03-20	Completed
Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Study to Evaluate the Efficacy, Safety & Tolerability of Two Doses of ACT-128800, an Oral S1P1 Receptor Agonist, Administered up to Twenty-eight Weeks in Patients With Moderate to S [NCT01208090]	Phase 2	326 participants (Actual)	Interventional	2010-10-31	Completed
Multicenter, Randomized, Double-blind, Parallel-group, Active-controlled, Superiority Study to Compare the Efficacy and Safety of Ponesimod to Teriflunomide in Subjects With Relapsing Multiple Sclerosis [NCT02425644]	Phase 3	1,133 participants (Actual)	Interventional	2015-06-04	Completed
Single-center, Open-label Study With 14C-labeled ACT-128800 to Investigate the Mass Balance, Pharmacokinetics, and Metabolism Following Single Oral Administration to Healthy Male Subjects [NCT02126956]	Phase 1	6 participants (Actual)	Interventional	2009-03-31	Completed
Czech Pharmaco-epidemiological Real World Data Study Focused on Effectiveness of Different Disease Modifying Drugs [NCT05762003]		17,478 participants (Actual)	Observational	2019-01-01	Completed
A Single-center, Double-blind, Randomized, Placebo- and Positive-controlled, Parallel-group, Multiple-dose, Up-titration Study of the Electrocardiographic Effects of Ponesimod in Healthy Male and Female Subjects [NCT02136888]	Phase 1	116 participants (Actual)	Interventional	2011-08-31	Completed
Multicenter, Non-comparative Extension of Study AC-058B301, to Investigate the Long-term Safety, Tolerability, and Control of Disease of Ponesimod 20 mg in Subjects With Relapsing Multiple Sclerosis [NCT03232073]	Phase 3	877 participants (Actual)	Interventional	2017-07-05	Active, not recruiting
Single-center, Open-label, Parallel-group Study to Evaluate the Pharmacokinetics, Tolerability, and Safety of a Single Dose of 40 mg ACT-128800 in Japanese and Caucasian Healthy Male and Female Subjects [NCT02223832]	Phase 1	20 participants (Actual)	Interventional	2009-02-28	Completed
Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group, Dose-finding Study to Evaluate the Efficacy, Safety, and Tolerability of Three Doses of ACT-128800, an Oral S1P1 Receptor Agonist, Administered for Twenty-four Weeks in Patients Wi [NCT01006265]	Phase 2	464 participants (Actual)	Interventional	2009-10-01	Completed
Single-center, Double-blind, Placebo-controlled, Randomized, Parallel-group, Up-titration Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Increasing Doses of ACT-128800 in Healthy Male and Female Subjects [NCT02029482]	Phase 1	16 participants (Actual)	Interventional	2010-04-30	Completed
Single-center, Open-label, Randomized, Two-way Crossover Study to Investigate the Absolute Bioavailability of a Single Oral Dose of Ponesimod in Healthy Male Subjects [NCT02068235]	Phase 1	17 participants (Actual)	Interventional	2014-08-31	Completed
Pregnancy Outcomes in Women Exposed to Diroximel Fumarate [NCT05688436]		1,178 participants (Anticipated)	Observational [Patient Registry]	2021-09-24	Recruiting
Multicenter, Randomized, Double-blind, Placebo-controlled, Phase IIa Study to Evaluate the Efficacy, Safety, and Tolerability of ACT-128800, an S1P1 Receptor Agonist, Administered for 6 Weeks to Subjects With Moderate to Severe Chronic Plaque Psoriasis [NCT00852670]	Phase 2	66 participants (Actual)	Interventional	2008-10-31	Completed
Multicenter, Randomized, Double-blind, Parallel-group Extension to Study AC-058B201 to Investigate the Long-term Safety, Tolerability, and Efficacy of Three Doses of Ponesimod, an Oral S1P1 Receptor Agonist, in Patients With Relapsing-remitting Multiple S [NCT01093326]	Phase 2	353 participants (Actual)	Interventional	2010-05-12	Completed
Determining the Effectiveness of earLy Intensive Versus Escalation Approaches for the Treatment of Relapsing-Remitting Multiple Sclerosis [NCT03535298]	Phase 4	800 participants (Anticipated)	Interventional	2019-01-03	Recruiting
A Pragmatic Trial to Evaluate the Intermediate-term Effects of Early, Aggressive Versus Escalation Therapy in People With Multiple Sclerosis [NCT03500328]		900 participants (Anticipated)	Interventional	2018-05-02	Recruiting
A Phase 2, Open-label, Single-arm, Intra-subject Dose-escalation Study to Investigate the Biological Activity, Safety, Tolerability, and Pharmacokinetics of Ponesimod in Subjects With Symptomatic Moderate or Severe Chronic GVHD Inadequately Responding to [NCT02461134]	Phase 2	1 participants (Actual)	Interventional	2016-09-29	Terminated(stopped due to Low recruitment)
A Phase 1, Open-label, Parallel-group Study to Assess the Effect of Steady-state Carbamazepine on the Pharmacokinetics of Ponesimod in Healthy Adult Participants [NCT05552196]	Phase 1	28 participants (Actual)	Interventional	2022-10-18	Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

Trial	Outcome
NCT01006265 (3) [back to overview]	Annualized Confirmed Relapse Rate
NCT01006265 (3) [back to overview]	Cumulative Number of New T1 Gadolinium-Enhancing (Gd+) Lesions on Magnetic Resonance Imaging (MRI) Scan From Week 12 to Week 24
NCT01006265 (3) [back to overview]	Number of Participants With First Confirmed Relapse as Assessed by Kaplan-Meier Estimate From Baseline to Week 24
NCT02425644 (5) [back to overview]	Annualized Confirmed Relapse Rate
NCT02425644 (5) [back to overview]	Change From Baseline in Fatigue-related Symptoms as Measured by the Symptoms Domain of the Fatigue Symptom and Impact Questionnaire-Relapsing Multiple Sclerosis (FSIQ-RMS) Score to Week 108
NCT02425644 (5) [back to overview]	Cumulative Number of Combined Unique Active Lesions (CUAL) Per Year From Baseline to Week 108
NCT02425644 (5) [back to overview]	12-Week Confirmed Disability Accumulation (CDA) Assessed From Baseline to EOS
NCT02425644 (5) [back to overview]	24-Week Confirmed Disability Accumulation (CDA) Assessed From Baseline to EOS
NCT02461134 (1) [back to overview]	Incident Rate of Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
NCT02907177 (4) [back to overview]	Annualized Confirmed Relapse Rate (ARR)
NCT02907177 (4) [back to overview]	Number of Participants With Adverse Events (AEs) as a Measure of Safety and Tolerability
NCT02907177 (4) [back to overview]	Percentage of Participants Experiencing a Confirmed Relapse as Assessed by Kaplan Meier Estimate at Week 96
NCT02907177 (4) [back to overview]	Percentage of Participants With 12-Week Confirmed Disability Accumulation (CDA) as Assessed by Kaplan Meier Estimate at Week 96

Annualized Confirmed Relapse Rate

Relapse: occurrence of acute episode of one or more new symptoms or worsened symptoms of Multiple Sclerosis (MS), not associated with fever/infection and lasting 24 hours after stable 30 days period. Confirmed relapse: increase from baseline at least 0.5 point Expanded Disability Status Scale (EDSS) score or increase of one point in one, two or three Functional Systems (FS), excluding bowel/bladder and cerebral/mental FS. EDSS and FS scores are based on neurological examination for assessing its impairment in MS. Among eight FS, seven are ordinal clinical rating scales ranging from 0-5 or 6 with higher scale indicating overall functional impairment assessing Visual, Brain Stem, Pyramidal, Cerebellar, Sensory, Bowel/Bladder and Cerebral functions. Rating individual FS scores is used to rate EDSS with information concerning gait and use of assistance. EDSS is ordinal clinical scale ranges 0 (normal neurological examination) to 10(death due to MS) (NCT01006265)
Timeframe: Up to 24 weeks

Intervention	Relapse per year (Mean)
Ponesimod 40 mg	0.224
Ponesimod 20 mg	0.396
Ponesimod 10 mg	0.297
Placebo	0.601

[back to top]

Cumulative Number of New T1 Gadolinium-Enhancing (Gd+) Lesions on Magnetic Resonance Imaging (MRI) Scan From Week 12 to Week 24

Cumulative Number of new T1 gadolinium-enhancing (Gd+) lesions per year on magnetic resonance imaging (MRI) scan from Week 12 to Week 24 were reported. Negative binomial (NB) regression analysis on Per protocol analysis set and imputation was applied for the missing data. Here, MS signifies multiple sclerosis. (NCT01006265)
Timeframe: From Week 12 to 24

Intervention	Lesions (Mean)
Ponesimod 40 mg	1.4
Ponesimod 20 mg	1.1
Ponesimod 10 mg	3.5
Placebo	6.2

[back to top]

Number of Participants With First Confirmed Relapse as Assessed by Kaplan-Meier Estimate From Baseline to Week 24

Relapse: occurrence of acute episode of one or more new symptoms or worsened symptoms of MS, not associated with fever/infection and lasting 24 hours after stable 30 days period. Confirmed relapse: increase from baseline at least 0.5 point Expanded Disability Status Scale (EDSS) score or increase of one point in one, two or three Functional Systems (FS), excluding bowel/bladder and cerebral/mental FS. EDSS and FS scores are based on neurological examination for assessing its impairment in MS. Among eight FS, seven are ordinal clinical rating scales ranging from 0-5 or 6 with higher scale indicating overall functional impairment assessing Visual, Brain Stem, Pyramidal, Cerebellar, Sensory, Bowel/Bladder and Cerebral functions. Rating individual FS scores is used to rate EDSS with information concerning gait and use of assistance. EDSS is ordinal clinical scale ranges 0 (normal neurological examination) to 10(death due to MS). Kaplan-Meier estimate used for Outcome Measure analysis. (NCT01006265)
Timeframe: Baseline to Week 24

Intervention	Participants (Count of Participants)
Ponesimod 40 mg	10
Ponesimod 20 mg	17
Ponesimod 10 mg	14
Placebo	25

[back to top]

Annualized Confirmed Relapse Rate

Relapse: occurrence of acute episode of one or more new symptoms or worsened symptoms of Multiple sclerosis (MS), not associated with fever/infection and lasting 24 hours after stable 30 days period. Confirmed relapse: increase from baseline at least 0.5 point Expanded Disability Status Scale (EDSS) score or increase of one point in one, two or three Functional Systems (FS), excluding bowel/bladder and cerebral/mental FS. EDSS and FS scores are based on neurological examination for assessing its impairment in MS. Among eight FS, seven are ordinal clinical rating scales ranging from 0-5 or 6 with higher scale indicates overall functional impairment assessing Visual,Brain Stem,Pyramidal,Cerebellar,Sensory, Bowel/Bladder and Cerebral functions. Rating individual FS scores is used to rate EDSS in conjunction with observations and information concerning gait and use of assistance. EDSS is ordinal clinical rating scale ranging from 0 (normal neurological examination) to 10(death due to MS). (NCT02425644)
Timeframe: From randomization to end of study (Week 108)

Intervention	relapses per year (Mean)
Ponesimod 20 mg	0.202
Teriflunomide 14 mg	0.290

[back to top]

Change From Baseline in Fatigue-related Symptoms as Measured by the Symptoms Domain of the Fatigue Symptom and Impact Questionnaire-Relapsing Multiple Sclerosis (FSIQ-RMS) Score to Week 108

The FSIQ-RMS is a 20-item Patient Reported Outcomes (PRO) measure to evaluate fatigue-related symptoms and the impacts of those symptoms on the lives of people. The FSIQ-RMS symptom domain (FSIQ-RMS-S) consists of seven items assessing fatigue-related symptoms daily with a recall period of 24 hours measured on an 11-point numeric rating scale; the (normalized) symptom domain score ranges from 0 to 100 with a higher score indicating greater fatigue. This domain was completed on 7 consecutive days. A negative change from baseline indicates an improvement in fatigue symptoms. (NCT02425644)
Timeframe: Baseline to Week 108

Intervention	score on scale (Least Squares Mean)
Ponesimod 20 mg	-0.01
Teriflunomide 14 mg	3.56

[back to top]

Cumulative Number of Combined Unique Active Lesions (CUAL) Per Year From Baseline to Week 108

CUALs was calculated as sum of new Gadolinium-enhanced (Gd+) T1 lesions plus new or enlarging T2 lesions (without double-counting of lesions) from baseline based on the Magnetic resonance imaging (MRI) scans up to Week 108. Average number of lesions per year were reported. (NCT02425644)
Timeframe: Baseline to Week 108

Intervention	lesions per year (Mean)
Ponesimod 20 mg	1.405
Teriflunomide 14 mg	3.164

[back to top]

12-Week Confirmed Disability Accumulation (CDA) Assessed From Baseline to EOS

A 12-week CDA was defined as an increase of at least 1.5 in Expanded Disability Status Scale (EDSS) for participants with a baseline EDSS score of 0.0 or an increase of at least 1.0 in EDSS for participants with a baseline EDSS score of 1.0 to 5.0, or an increase of at least 0.5 in EDSS for participants with a baseline EDSS score greater than or equal to (>=) 5.5, which was confirmed after 12 weeks. Baseline EDSS was defined as the last EDSS score recorded prior to randomization. EDSS is an ordinal clinical rating scale ranging from 0 (normal neurological examination) to 10 (death due to MS). (NCT02425644)
Timeframe: Baseline to Week 60 and 108 Weeks

Intervention	Percentage of Participants (Number)
	60 Weeks- from Kaplan Meier estimates	108 Weeks- from Kaplan Meier estimates
Ponesimod 20 mg	7.6	10.8
Teriflunomide 14 mg	8.3	13.2

[back to top]

24-Week Confirmed Disability Accumulation (CDA) Assessed From Baseline to EOS

A 24-week CDA was defined as an increase of at least 1.5 in EDSS for participants with a baseline EDSS score of 0.0 or an increase of at least 1.0 in EDSS for participants with a baseline EDSS score of 1.0 to 5.0, or an increase of at least 0.5 in EDSS for participants with a baseline EDSS score >= 5.5, which was confirmed after 24 weeks. Baseline EDSS was defined as the last EDSS score recorded prior to randomization. The EDSS is an ordinal scale ranging from 0 (normal neurological exam) to 10 (death to MS). (NCT02425644)
Timeframe: Baseline to 60 Weeks and 108 Weeks

Intervention	Percentage of Participants (Number)
	60 Weeks- from Kaplan Meier estimates	108 Weeks- from Kaplan Meier estimates
Ponesimod 20 mg	6.3	8.7
Teriflunomide 14 mg	6.9	10.5

[back to top]

Incident Rate of Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

This outcome measure reports the occurrence of adverse events (AEs), and serious adverse events (SAEs) during the treatment period and the follow-up period, and AEs leading to premature discontinuation of study drug. A treatment-emergent AE is any AE temporally associated with the use of study treatment whether or not considered by the investigator as related to study treatment. (NCT02461134)
Timeframe: From the first study drug intake up to 30 days after last study drug intake (Week 24)

Intervention	Participants (Count of Participants)
	Participants with AEs	Participants with SAEs	Participants discontinued prematurely study drug
Ponesimod	1	1	1

[back to top]

Annualized Confirmed Relapse Rate (ARR)

Relapse: occurrence of acute episode of one or more new or worsened symptoms of Multiple sclerosis (MS), not associated with fever/infection and lasting 24 hours after stable 30 days period. Confirmed relapse: increase from baseline at least 0.5 point Expanded Disability Status Scale (EDSS) score or increase of one point in one, two or three Functional Systems (FS), excluding bowel/bladder and cerebral/mental FS. EDSS and FS scores are based on neurological examination for assessing its impairment in MS. Among eight FS, seven are ordinal clinical rating scales ranging from 0-5 or 6 with higher scale indicates overall functional impairment assessing Visual, Brain Stem, Pyramidal, Cerebellar, Sensory, Bowel/Bladder and Cerebral functions. Rating individual FS scores is used to rate EDSS in conjunction with observations and information concerning gait and use of assistance. EDSS is ordinal clinical rating scale ranging from 0 (normal neurological examination) to 10(death due to MS). (NCT02907177)
Timeframe: Through study completion, an average of 68 weeks

Intervention	Relapses per year (Mean)
Ponesimod Plus Dimethyl Fumarate (DMF)	0.237
Placebo Plus Dimethyl Fumarate (DMF)	0.187

[back to top]

Number of Participants With Adverse Events (AEs) as a Measure of Safety and Tolerability

An AE is any untoward medical event that occurs in a participants administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. (NCT02907177)
Timeframe: Up to 147 Weeks

Intervention	Participants (Count of Participants)
Ponesimod Plus Dimethyl Fumarate (DMF)	48
Placebo Plus Dimethyl Fumarate (DMF)	53

[back to top]

Percentage of Participants Experiencing a Confirmed Relapse as Assessed by Kaplan Meier Estimate at Week 96

Percentage of participants experiencing a confirmed relapse as assessed by Kaplan Meier estimate at week 96 was reported. The time to first confirmed relapse (in days) is defined as [Date of first confirmed relapse minus Date of randomization plus 1] in days. Relapse: Occurrence of acute episode of one or more new symptoms or worsened symptoms of Multiple sclerosis (MS), not related with fever/infection and lasting 24 hours after 30 days stable period. (NCT02907177)
Timeframe: Week 96

Intervention	Percentage of Participants (Number)
Ponesimod Plus Dimethyl Fumarate (DMF)	33.6
Placebo Plus Dimethyl Fumarate (DMF)	25.7

[back to top]

Percentage of Participants With 12-Week Confirmed Disability Accumulation (CDA) as Assessed by Kaplan Meier Estimate at Week 96

Percentage of participants with 12-week CDA as assessed by Kaplan Meier estimate at week 96 was defined as an increase of at least 1.5 in Expanded Disability Status Scale (EDSS) for participants with a baseline EDSS score of 0.0 or an increase of at least 1.0 in EDSS for participants with a baseline EDSS score of 1.0 to 5.0, or an increase of at least 0.5 in EDSS for participants with a baseline EDSS score greater than or equal to (>=) 5.5, which was confirmed after 12 weeks. Baseline EDSS was defined as the last EDSS score recorded prior to randomization. EDSS is an ordinal clinical rating scale ranging from 0 (normal neurological examination) to 10 (death due to MS). (NCT02907177)
Timeframe: Week 96

Intervention	Percentage of participants with a CDA. (Number)
Ponesimod Plus Dimethyl Fumarate (DMF)	18.7
Placebo Plus Dimethyl Fumarate (DMF)	11.9

[back to top]

Substance	Relationship Strength	Studies	Trials	Classes	Roles
niacinamide nicotinamide : A pyridinecarboxamide that is pyridine in which the hydrogen at position 3 is replaced by a carboxamide group.	3.23	1	0	pyridine alkaloid; pyridinecarboxamide; vitamin B3	anti-inflammatory agent; antioxidant; cofactor; EC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitor; EC 3.5.1.98 (histone deacetylase) inhibitor; Escherichia coli metabolite; geroprotector; human urinary metabolite; metabolite; mouse metabolite; neuroprotective agent; Saccharomyces cerevisiae metabolite; Sir2 inhibitor
thalidomide Thalidomide: A piperidinyl isoindole originally introduced as a non-barbiturate hypnotic, but withdrawn from the market due to teratogenic effects. It has been reintroduced and used for a number of immunological and inflammatory disorders. Thalidomide displays immunosuppressive and anti-angiogenic activity. It inhibits release of TUMOR NECROSIS FACTOR-ALPHA from monocytes, and modulates other cytokine action.. thalidomide : A racemate comprising equimolar amounts of R- and S-thalidomide.. 2-(2,6-dioxopiperidin-3-yl)-1H-isoindole-1,3(2H)-dione : A dicarboximide that is isoindole-1,3(2H)-dione in which the hydrogen attached to the nitrogen is substituted by a 2,6-dioxopiperidin-3-yl group.	4.16	2	0	phthalimides; piperidones
ethinyl estradiol Ethinyl Estradiol: A semisynthetic alkylated ESTRADIOL with a 17-alpha-ethinyl substitution. It has high estrogenic potency when administered orally, and is often used as the estrogenic component in ORAL CONTRACEPTIVES.. 17alpha-ethynylestradiol : A 3-hydroxy steroid that is estradiol substituted by a ethynyl group at position 17. It is a xenoestrogen synthesized from estradiol and has been shown to exhibit high estrogenic potency on oral administration.	3.48	1	1	17-hydroxy steroid; 3-hydroxy steroid; terminal acetylenic compound	xenoestrogen
norethindrone Norethindrone: A synthetic progestational hormone with actions similar to those of PROGESTERONE but functioning as a more potent inhibitor of ovulation. It has weak estrogenic and androgenic properties. The hormone has been used in treating amenorrhea, functional uterine bleeding, endometriosis, and for CONTRACEPTION.. norethisterone : A 17beta-hydroxy steroid that is testosterone in which the hydrogen at position 17 is replaced by an ethynyl group and in which the methyl group attached to position 10 is replaced by hydrogen.	3.48	1	1	17beta-hydroxy steroid; 3-oxo-Delta(4) steroid; terminal acetylenic compound; tertiary alcohol	progestin; synthetic oral contraceptive
pyrroles 1H-pyrrole : A tautomer of pyrrole that has the double bonds at positions 2 and 4.. pyrrole : A five-membered monocyclic heteroarene comprising one NH and four CH units which forms the parent compound of the pyrrole group of compounds. Its five-membered ring structure has three tautomers. A 'closed class'.. azole : Any monocyclic heteroarene consisting of a five-membered ring containing nitrogen. Azoles can also contain one or more other non-carbon atoms, such as nitrogen, sulfur or oxygen.	4.16	2	0	pyrrole; secondary amine
thiophenes Thiophenes: A monocyclic heteroarene furan in which the oxygen atom is replaced by a sulfur.. thiophenes : Compounds containing at least one thiophene ring.	2.49	2	0	mancude organic heteromonocyclic parent; monocyclic heteroarene; thiophenes; volatile organic compound	non-polar solvent
adamantane Adamantane: A tricyclo bridged hydrocarbon.	3.23	1	0	adamantanes; polycyclic alkane
thiazoles [no description available]	15.64	58	19	1,3-thiazoles; mancude organic heteromonocyclic parent; monocyclic heteroarene
thiazolidines Thiazolidines: Reduced (protonated) form of THIAZOLES. They can be oxidized to THIAZOLIDINEDIONES.	3.87	2	1	thiazolidine
paclitaxel Taxus: Genus of coniferous yew trees or shrubs, several species of which have medicinal uses. Notable is the Pacific yew, Taxus brevifolia, which is used to make the anti-neoplastic drug taxol (PACLITAXEL).	2.1	1	0	taxane diterpenoid; tetracyclic diterpenoid	antineoplastic agent; human metabolite; metabolite; microtubule-stabilising agent
adenosine quinquefolan B: isolated from roots of Panax quinquefolium L.; RN not in Chemline 10/87; RN from Toxlit	3.23	1	0	adenosines; purines D-ribonucleoside	analgesic; anti-arrhythmia drug; fundamental metabolite; human metabolite; vasodilator agent
fingolimod hydrochloride Fingolimod Hydrochloride: A sphingosine-derivative and IMMUNOSUPPRESSIVE AGENT that blocks the migration and homing of LYMPHOCYTES to the CENTRAL NERVOUS SYSTEM through its action on SPHINGOSINE 1-PHOSPHATE RECEPTORS. It is used in the treatment of MULTIPLE SCLEROSIS.. fingolimod hydrochloride : The hydrochloride salt of 2-amino-2-[2-(4-octylphenyl) ethyl]-1,3-propanediol (fingolimod).	5.93	4	0	hydrochloride	immunosuppressive agent; prodrug; sphingosine-1-phosphate receptor agonist
fingolimod fingolimod : An aminodiol that consists of propane-1,3-diol having amino and 2-(4-octylphenyl)ethyl substituents at the 2-position. It is a sphingosine 1-phosphate receptor modulator used for the treatment of relapsing-remitting multiple sclerosis. A prodrug, fingolimod is phosphorylated by sphingosine kinase to active metabolite fingolimod-phosphate, a structural analogue of sphingosine 1-phosphate.	4.13	2	0	aminodiol; primary amino compound	antineoplastic agent; CB1 receptor antagonist; immunosuppressive agent; prodrug; sphingosine-1-phosphate receptor agonist
n(6)-(3-iodobenzyl)-5'-n-methylcarboxamidoadenosine N(6)-(3-iodobenzyl)-5'-N-methylcarboxamidoadenosine: structure given in first source; a selective A(3) adenosine receptor agonist. 3-iodobenzyl-5'-N-methylcarboxamidoadenosine : A derivative of adenosine in which the 5'-hydroxymethyl group is replaced by N-ethylcarboxamido and one of the hydrogens of the exocyclic amino function is substituted by a 3-iodobenzyl group.	3.23	1	0	adenosines; monocarboxylic acid amide; organoiodine compound	adenosine A3 receptor agonist
moxifloxacin Moxifloxacin: A fluoroquinolone that acts as an inhibitor of DNA TOPOISOMERASE II and is used as a broad-spectrum antibacterial agent.. moxifloxacin : A quinolone that consists of 4-oxo-1,4-dihydroquinoline-3-carboxylic acid bearing a cyclopropyl substituent at position 1, a fluoro substitiuent at position 6, a (4aS,7aS)-octahydro-6H-pyrrolo[3,4-b]pyridin-6-yl group at position 7 and a methoxy substituent at position 8. A member of the fluoroquinolone class of antibacterial agents.	4.41	1	1	aromatic ether; cyclopropanes; fluoroquinolone antibiotic; pyrrolidinopiperidine; quinolinemonocarboxylic acid; quinolone antibiotic; quinolone	antibacterial drug
organophosphonates hydrogenphosphite : A divalent inorganic anion resulting from the removal of a proton from two of the hydroxy groups of phosphorous acid.	2.1	1	0	divalent inorganic anion; phosphite ion
dimethyl fumarate [no description available]	3.99	1	1	diester; enoate ester; methyl ester	antipsoriatic; immunomodulator
sew2871 SEW2871: structure in first source	2.49	2	0	oxadiazole; ring assembly
sphingosine sphing-4-enine : A sphingenine in which the C=C double bond is located at the 4-position.. sphingenine : A 2-aminooctadecene-1,3-diol having (2S,3R)-configuration.. sphingoid : Sphinganine, its homologs and stereoisomers, and the hydroxy and unsaturated derivatives of these compounds.. 2-aminooctadec-4-ene-1,3-diol : A 2-aminooctadecene-1,3-diol having its double bond at position 4.	9.84	5	0	sphing-4-enine	human metabolite; mouse metabolite
sphingosine 1-phosphate sphingosine 1-phosphate: RN given refers to (R-(R,S-(E)))-isomer; RN for cpd without isomeric designation not available 8/89. sphingosine 1-phosphate : A phosphosphingolipid that consists of sphingosine having a phospho group attached at position 1	4.29	5	0	sphingoid 1-phosphate	mouse metabolite; signalling molecule; sphingosine-1-phosphate receptor agonist; T-cell proliferation inhibitor; vasodilator agent
tofacitinib tofacitinib : A pyrrolopyrimidine that is pyrrolo[2,3-d]pyrimidine substituted at position 4 by an N-methyl,N-(1-cyanoacetyl-4-methylpiperidin-3-yl)amino moiety. Used as its citrate salt to treat moderately to severely active rheumatoid arthritis.	4.16	2	0	N-acylpiperidine; nitrile; pyrrolopyrimidine; tertiary amino compound	antirheumatic drug; EC 2.7.10.2 (non-specific protein-tyrosine kinase) inhibitor
oxadiazoles Oxadiazoles: Compounds containing five-membered heteroaromatic rings containing two carbons, two nitrogens, and one oxygen atom which exist in various regioisomeric forms.	7.3	6	0
cs 0777 CS 0777: a sphingosine-1-phosphate receptor modulator	3.18	1	0
apremilast [no description available]	4.16	2	0	aromatic ether; N-acetylarylamine; phthalimides; sulfone	non-steroidal anti-inflammatory drug; phosphodiesterase IV inhibitor
baricitinib [no description available]	3.23	1	0	azetidines; nitrile; pyrazoles; pyrrolopyrimidine; sulfonamide	anti-inflammatory agent; antirheumatic drug; antiviral agent; EC 2.7.10.2 (non-specific protein-tyrosine kinase) inhibitor; immunosuppressive agent
piperidines Piperidines: A family of hexahydropyridines.	4.16	2	0
siponimod siponimod: S1P receptor modulator	7.68	6	0
incb039110 INCB039110: a JAK1 inhibitor; structure in first source	3.23	1	0
3-amino-4-(3-hexylphenylamino)-4-oxobutylphosphonic acid 3-amino-4-(3-hexylphenylamino)-4-oxobutylphosphonic acid: W146 is the (R)-isomer; structure in first source	2.1	1	0
teriflunomide [no description available]	6.52	4	3	(trifluoromethyl)benzenes; aromatic amide; enamide; enol; nitrile; secondary carboxamide	drug metabolite; EC 1.3.98.1 [dihydroorotate oxidase (fumarate)] inhibitor; hepatotoxic agent; non-steroidal anti-inflammatory drug; tyrosine kinase inhibitor
guanosine 5'-o-(3-thiotriphosphate) Guanosine 5'-O-(3-Thiotriphosphate): Guanosine 5'-(trihydrogen diphosphate), monoanhydride with phosphorothioic acid. A stable GTP analog which enjoys a variety of physiological actions such as stimulation of guanine nucleotide-binding proteins, phosphoinositide hydrolysis, cyclic AMP accumulation, and activation of specific proto-oncogenes.	2.06	1	0	nucleoside triphosphate analogue

Condition	Relationship Strength	Studies	Trials
Acute Relapsing Multiple Sclerosis [description not available]	12.63	19	9
Multiple Sclerosis, Relapsing-Remitting The most common clinical variant of MULTIPLE SCLEROSIS, characterized by recurrent acute exacerbations of neurologic dysfunction followed by partial or complete recovery. Common clinical manifestations include loss of visual (see OPTIC NEURITIS), motor, sensory, or bladder function. Acute episodes of demyelination may occur at any site in the central nervous system, and commonly involve the optic nerves, spinal cord, brain stem, and cerebellum. (Adams et al., Principles of Neurology, 6th ed, pp903-914)	12.63	19	9
Recrudescence [description not available]	7.36	7	3
MS (Multiple Sclerosis) [description not available]	12.66	24	4
Multiple Sclerosis An autoimmune disorder mainly affecting young adults and characterized by destruction of myelin in the central nervous system. Pathologic findings include multiple sharply demarcated areas of demyelination throughout the white matter of the central nervous system. Clinical manifestations include visual loss, extra-ocular movement disorders, paresthesias, loss of sensation, weakness, dysarthria, spasticity, ataxia, and bladder dysfunction. The usual pattern is one of recurrent attacks followed by partial recovery (see MULTIPLE SCLEROSIS, RELAPSING-REMITTING), but acute fulminating and chronic progressive forms (see MULTIPLE SCLEROSIS, CHRONIC PROGRESSIVE) also occur. (Adams et al., Principles of Neurology, 6th ed, p903)	12.66	24	4
Breathlessness [description not available]	2.6	1	0
Dyspnea Difficult or labored breathing.	7.6	1	0
Acute Confusional Senile Dementia [description not available]	2.6	1	0
Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases.	2.6	1	0
Alzheimer Disease A degenerative disease of the BRAIN characterized by the insidious onset of DEMENTIA. Impairment of MEMORY, judgment, attention span, and problem solving skills are followed by severe APRAXIAS and a global loss of cognitive abilities. The condition primarily occurs after age 60, and is marked pathologically by severe cortical atrophy and the triad of SENILE PLAQUES; NEUROFIBRILLARY TANGLES; and NEUROPIL THREADS. (From Adams et al., Principles of Neurology, 6th ed, pp1049-57)	2.6	1	0
Hepatitis B Virus Infection [description not available]	7.31	1	0
Hepatitis B INFLAMMATION of the LIVER in humans caused by a member of the ORTHOHEPADNAVIRUS genus, HEPATITIS B VIRUS. It is primarily transmitted by parenteral exposure, such as transfusion of contaminated blood or blood products, but can also be transmitted via sexual or intimate personal contact.	7.31	1	0
Disease Exacerbation [description not available]	4.62	1	1
Local Neoplasm Recurrence [description not available]	4.62	1	1
Allergic Encephalomyelitis [description not available]	2.31	1	0
Acute Brain Injuries [description not available]	2.31	1	0
Brain Inflammation [description not available]	2.31	1	0
Hemorrhage, Subarachnoid [description not available]	2.31	1	0
Brain Injuries Acute and chronic (see also BRAIN INJURIES, CHRONIC) injuries to the brain, including the cerebral hemispheres, CEREBELLUM, and BRAIN STEM. Clinical manifestations depend on the nature of injury. Diffuse trauma to the brain is frequently associated with DIFFUSE AXONAL INJURY or COMA, POST-TRAUMATIC. Localized injuries may be associated with NEUROBEHAVIORAL MANIFESTATIONS; HEMIPARESIS, or other focal neurologic deficits.	2.31	1	0
Encephalitis Inflammation of the BRAIN due to infection, autoimmune processes, toxins, and other conditions. Viral infections (see ENCEPHALITIS, VIRAL) are a relatively frequent cause of this condition.	2.31	1	0
Subarachnoid Hemorrhage Bleeding into the intracranial or spinal SUBARACHNOID SPACE, most resulting from INTRACRANIAL ANEURYSM rupture. It can occur after traumatic injuries (SUBARACHNOID HEMORRHAGE, TRAUMATIC). Clinical features include HEADACHE; NAUSEA; VOMITING, nuchal rigidity, variable neurological deficits and reduced mental status.	7.31	1	0
Diseases of Immune System [description not available]	4.15	1	0
Nervous System Disorders [description not available]	4.15	1	0
Immune System Diseases Disorders caused by abnormal or absent immunologic mechanisms, whether humoral, cell-mediated, or both.	4.15	1	0
Nervous System Diseases Diseases of the central and peripheral nervous system. This includes disorders of the brain, spinal cord, cranial nerves, peripheral nerves, nerve roots, autonomic nervous system, neuromuscular junction, and muscle.	4.15	1	0
Palmoplantaris Pustulosis [description not available]	7.63	6	2
Psoriasis A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis.	7.63	6	2
Autoimmune Disease [description not available]	3.45	2	0
Autoimmune Diseases Disorders that are characterized by the production of antibodies that react with host tissues or immune effector cells that are autoreactive to endogenous peptides.	3.45	2	0
Clinically Isolated CNS Demyelinating Syndrome [description not available]	6.98	4	0
Demyelinating Diseases Diseases characterized by loss or dysfunction of myelin in the central or peripheral nervous system.	6.98	4	0
Alveolitis, Fibrosing [description not available]	2.08	1	0
Pulmonary Fibrosis A process in which normal lung tissues are progressively replaced by FIBROBLASTS and COLLAGEN causing an irreversible loss of the ability to transfer oxygen into the bloodstream via PULMONARY ALVEOLI. Patients show progressive DYSPNEA finally resulting in death.	2.08	1	0
Atrioventricular Conduction Block [description not available]	2.08	1	0
Atrioventricular Block Impaired impulse conduction from HEART ATRIA to HEART VENTRICLES. AV block can mean delayed or completely blocked impulse conduction.	2.08	1	0
Autoimmune Diabetes [description not available]	7.08	1	0
Diabetes Mellitus, Type 1 A subtype of DIABETES MELLITUS that is characterized by INSULIN deficiency. It is manifested by the sudden onset of severe HYPERGLYCEMIA, rapid progression to DIABETIC KETOACIDOSIS, and DEATH unless treated with insulin. The disease may occur at any age, but is most common in childhood or adolescence.	2.08	1	0
Nerve Pain [description not available]	2.1	1	0
Neuralgia Intense or aching pain that occurs along the course or distribution of a peripheral or cranial nerve.	2.1	1	0
Body Weight The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms.	2.1	1	0
Chronic Illness [description not available]	4.4	1	1
Chronic Disease Diseases which have one or more of the following characteristics: they are permanent, leave residual disability, are caused by nonreversible pathological alteration, require special training of the patient for rehabilitation, or may be expected to require a long period of supervision, observation, or care (Dictionary of Health Services Management, 2d ed). For epidemiological studies chronic disease often includes HEART DISEASES; STROKE; CANCER; and diabetes (DIABETES MELLITUS, TYPE 2).	4.4	1	1
Electrocardiogram QT Prolonged [description not available]	4.41	1	1
Long QT Syndrome A condition that is characterized by episodes of fainting (SYNCOPE) and varying degree of ventricular arrhythmia as indicated by the prolonged QT interval. The inherited forms are caused by mutation of genes encoding cardiac ion channel proteins. The two major forms are ROMANO-WARD SYNDROME and JERVELL-LANGE NIELSEN SYNDROME.	4.41	1	1
Kidney Failure A severe irreversible decline in the ability of kidneys to remove wastes, concentrate URINE, and maintain ELECTROLYTE BALANCE; BLOOD PRESSURE; and CALCIUM metabolism.	3.51	1	1
Liver Dysfunction [description not available]	3.51	1	1
Liver Diseases Pathological processes of the LIVER.	3.51	1	1
Renal Insufficiency Conditions in which the KIDNEYS perform below the normal level in the ability to remove wastes, concentrate URINE, and maintain ELECTROLYTE BALANCE; BLOOD PRESSURE; and CALCIUM metabolism. Renal insufficiency can be classified by the degree of kidney damage (as measured by the level of PROTEINURIA) and reduction in GLOMERULAR FILTRATION RATE.	3.51	1	1
Psoriasis Arthropathica [description not available]	3.04	1	0
Arthritis, Psoriatic A type of inflammatory arthritis associated with PSORIASIS, often involving the axial joints and the peripheral terminal interphalangeal joints. It is characterized by the presence of HLA-B27-associated SPONDYLARTHROPATHY, and the absence of rheumatoid factor.	3.04	1	0
Dermatoses [description not available]	3.06	1	0
Skin Diseases Diseases involving the DERMIS or EPIDERMIS.	3.06	1	0
Adjuvant Arthritis [description not available]	2.06	1	0
Delayed Hypersensitivity [description not available]	2.06	1	0
Innate Inflammatory Response [description not available]	2.06	1	0
Inflammation A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.	7.06	1	0

chemdatabank.com

ponesimod

Description

Cross-References

Synonyms (47)

Research Excerpts

Overview

Actions

Treatment

Toxicity

Pharmacokinetics

Bioavailability

Dosage Studied

Protein Targets (2)

Inhibition Measurements

Activation Measurements

Biological Processes (37)

Molecular Functions (7)

Ceullar Components (7)

Bioassays (18)

Research

Studies (62)

Market Indicators

Research Demand Index: 63.39

Study Types

Clinical Trials (19)

Trial Overview

Trial Outcomes

Annualized Confirmed Relapse Rate

Cumulative Number of New T1 Gadolinium-Enhancing (Gd+) Lesions on Magnetic Resonance Imaging (MRI) Scan From Week 12 to Week 24

Number of Participants With First Confirmed Relapse as Assessed by Kaplan-Meier Estimate From Baseline to Week 24

Annualized Confirmed Relapse Rate

Change From Baseline in Fatigue-related Symptoms as Measured by the Symptoms Domain of the Fatigue Symptom and Impact Questionnaire-Relapsing Multiple Sclerosis (FSIQ-RMS) Score to Week 108

Cumulative Number of Combined Unique Active Lesions (CUAL) Per Year From Baseline to Week 108

12-Week Confirmed Disability Accumulation (CDA) Assessed From Baseline to EOS

24-Week Confirmed Disability Accumulation (CDA) Assessed From Baseline to EOS

Incident Rate of Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

Annualized Confirmed Relapse Rate (ARR)

Number of Participants With Adverse Events (AEs) as a Measure of Safety and Tolerability

Percentage of Participants Experiencing a Confirmed Relapse as Assessed by Kaplan Meier Estimate at Week 96

Percentage of Participants With 12-Week Confirmed Disability Accumulation (CDA) as Assessed by Kaplan Meier Estimate at Week 96

Related Drugs (31)

Related Conditions (56)