Latent Variable Indirect Response Modeling of Cendakimab Exposure-Response for Longitudinal Dysphagia Days Using a Combined Uniform-Binomial Likelihood Framework.

To characterize the relationship between cendakimab exposure and the longitudinal efficacy endpoint dysphagia days (DD), E-R analyses were performed using data from the EE-001 study (N = 427) with eosinophilic esophagitis. DD-a bounded, discrete endpoint assessed over 14-day period via modified daily symptom diary (mDSD)-was modeled using a latent variable indirect response (IDR) model coupled with a combined uniform-binomial (CUB) distribution. The latent variable, representing the underlying disease status, was dynamically modulated by placebo and drug effects (a function of individual-predicted exposure) to govern the binomial probability of DD, while the uniform component captured the residual variability in patient-reported outcomes. Inter-individual variability was estimated for baseline DD, maximum placebo effect, and maximum drug effect. Covariates, including steroid inadequate response or intolerance (Steroid IR/I) status and baseline DD, were incorporated in the final model based on the clinical relevance. The estimated placebo half-life was ~28 weeks, estimated EC