The following is a summary of “A quantitative systems pharmacology workflow toward optimal design and biomarker stratification of atopic dermatitis clinical trials,” published in the May 2024 issue of Allergy & Immunology by Go, et al.
The complexity of atopic dermatitis (AD) phenotypes and trial design options pose challenges to the development of effective drugs. In a study, researchers used simulations to optimize the trial design for AD.
A quantitative systems pharmacology model of AD and standard of care (SoC) treatments was constructed. A phenotypically diverse virtual population was generated based on known relationships between AD biomarkers and disease severity. The population was calibrated using disease severity evolution under SoC regimens.
The workflow was applied to the immunomodulator OM-85, which is currently under investigation for AD treatment. The investigational treatment model was calibrated with the efficacy profile of an existing trial, enriching it with plausible marker levels and dynamics. Trial outcomes were found to be more sensitive to the choice of endpoint than to the dosing regimen or patient selection. Model-based responder enrichment could increase the expected effect size. A global sensitivity analysis revealed that only a limited subset of baseline biomarkers is needed to predict drug response across the virtual population.
The quantitative systems pharmacology workflow, informed by knowledge of marker-severity relationships and SoC efficacy, can be tailored to optimize trial protocol parameters and biomarker stratification for specific development cases. It held promise as a powerful tool for model-informed AD drug development and personalized medicine.
Reference: jacionline.org/article/S0091-6749(24)00158-1/abstract