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Updated: Feb 18, 2026

A Pipeline to Investigate the Structures and Signaling Pathways of Sphingosine 1-Phosphate Receptors
Published on: June 8, 2022
Modeling clinical efficacy of the S1P receptor modulator ponesimod in psoriasis
Andreas Krause1, Daniele D'Ambrosio2, Jasper Dingemanse1
1Department of Clinical Pharmacology, Actelion Pharmaceuticals Ltd, Allschwil, Switzerland.
Background:
Ponesimod is currently the only S1P receptor modulator studied in psoriasis. In a dose-finding study, the active doses showed similar efficacy.
Objective:
Prediction of efficacy at lower doses to aid clinical phase 3 planning with respect to dose selection, duration of treatment, and patient inclusion criteria based on pharma-co-kinetic/pharmacodynamic (PK/PD) modeling and simulation.
Methods:
The dose-finding study treated 326 patients (67 on placebo, 126 on 20mg, and 133 on 40mg) over 16 weeks. PK/PD modeling of steady-state trough concentrations and longitudinal PASI scores was employed to characterize data and simulate scenarios.
Results:
PASI score continually decreased with time on ponesimod treatment, reaching a plateau at 16 weeks. Absolute and relative (percent) PASI score change was larger in patients with higher PASI score at baseline. Doses below 10mg were predicted to show lower efficacy than doses of 10mg and higher.
Conclusion:
Concentration-response modeling was able to predict the efficacy of doses that were not studied. In psoriasis patients, a dose of 10mg (not administered in the study) was predicted to show efficacy similar to 20mg. Disease status (PASI score at baseline) as study inclusion criterion has pronounced influence on study outcome.
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