Model-Informed Drug Development for Ligelizumab in Patients With Chronic Spontaneous Urticaria.

Model-informed drug development (MIDD) has been increasingly applied to guide decision-making, ameliorate efficiency, and enhance the likelihood of successful trials. The development of ligelizumab, a humanized anti-IgE monoclonal antibody, in chronic spontaneous urticaria (CSU) illustrated how MIDD can be applied to support central aspects of drug development, such as dose selection and trial design, pediatric drug development and extrapolation, generation of evidence to support potential labeling, optimizing treatment outcomes, and enhancing patient access. In this manuscript, we provide an overview of the key modeling and simulation analyses that were part of the MIDD approach for the development of ligelizumab in CSU and how they were staggered around the availability of interim and final data from the Phase 2 and Phase 3 studies. Furthermore, we present details of the non-linear mixed-effects models characterizing the population pharmacokinetics and exposure-response relationship of ligelizumab for efficacy in adolescent and adult patients with CSU.