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 50 was 76.5 μg/mL, corresponding to an EC 90 of ~688 μg/mL, indicating steepness of the E max curve. Model‐based simulations showed that both 360 mg QW and QW‐to‐Q2W regimens reduced DD compared to placebo at Week 48, with mean reductions of ~1.65 and ~1.36 days, respectively. Covariate‐stratified simulations suggested consistent responses across sex, age, and race. Steroid IR/I and baseline DD influenced treatment response magnitude but did not warrant dose modification. These findings support QW‐to‐Q2W as an effective maintenance posology and the utility of latent variable IDR models with appropriate likelihoods for modeling bounded, discrete longitudinal endpoints in E–R analyses.