Description
Orismilast is a novel oral selective inhibitor of phosphodiesterase 4B and 4D subtypes (PDE4B/D) in clinical development for treatment of atopic dermatitis (AD) and other inflammatory skin conditions. Herein, we describe a pharmacokinetic/pharmacodynamic (PK/PD) analysis comparing predicted exposure data of orismilast and apremilast in AD patients and place these data in the context of their IL-13 secretion data generated in a human whole-blood assay.A PK/PD assessment of orismilast and apremilast in AD was performed. In a human whole blood assay, the levels needed to inhibit IL-13 production were measured for orismilast and apremilast head-to-head. These data were then contextualized with simulated exposure of clinically relevant doses of the two drugs.The analysis shows that orismilast has potential to significantly inhibit IL-13 production at all three clinical doses trialed in AD (20 mg bid, 30 mg bid, and 40 mg bid) as the drug has a predicted C plasma concentration exceeding the IL-13 IC value of the human whole-blood assay and a predicted C above the IL-13 IC value. Apremilast, in contrast, is predicted to reach C plasma concentrations below the IL-13 IC value for both doses (30 mg bid and 40 mg bid) and only exceeding the IL-13 IC value at peak concentrations for the highest dose.The outcome of the analysis supports the observed clinical effect of orismilast in patients with AD and could explain the lack of efficacy of apremilast in the same indication.
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