The Use of Quantitative Systems Pharmacology-based Digital Twins to Support Drug Development in Rare Diseases

Quantitative Systems Pharmacology (QSP) models hold great promise to support drug development, especially in rare diseases where high phenotypic heterogeneity and low patient number are common. QSP model-based digital twins allow the combination of mechanistic knowledge on the pathophysiology and the drug’s mechanism of action with individual patient demographics to describe a patient’s biomarkers and clinical endpoint responses. Since digital twins contain descriptions of processes that are biologically interpretable, they provide a way to gain insight into observed heterogeneity of disease burden and variability in drug efficacy. This approach can be used to predict efficacy of alternative drug regimens in different patient subpopulations. Also, use of digital twins provides a systematic method to quantify the degree of similarity of disease and drug response in different patient subpopulations. This presentation will describe examples where a QSP-based digital twin approach supported drug development in rare indications.