Latent Variable Indirect Response Modeling of Cendakimab Exposure-Response for Longitudinal Dysphagia Days Using a...

Area of Science:

• Pharmacometrics
• Clinical Pharmacology
• Gastroenterology

Background:

• Eosinophilic esophagitis (EoE) is a chronic inflammatory disease characterized by dysphagia.
• Understanding the exposure-response relationship is crucial for optimizing treatment strategies.

Purpose of the Study:

• To characterize the exposure-response (E-R) relationship of cendakimab on dysphagia days (DD) in EoE patients.
• To evaluate the efficacy of different cendakimab dosing regimens.

Main Methods:

• Utilized data from the EE-001 study (N=427) with eosinophilic esophagitis.
• Employed a latent variable indirect response (IDR) model with a combined uniform-binomial (CUB) distribution to analyze DD.
• Incorporated covariates such as steroid inadequate response/intolerance (Steroid IR/I) and baseline DD.

Main Results:

• Cendakimab exposure was linked to reduced DD.
• Estimated EC50 and EC90 values indicated a steep Emax curve.
• Simulations showed 360 mg QW and QW-to-Q2W regimens reduced DD by ~1.65 and ~1.36 days vs. placebo at Week 48.
• Consistent responses observed across demographics; Steroid IR/I and baseline DD influenced magnitude but not dose.

Conclusions:

• The QW-to-Q2W maintenance posology is effective for cendakimab in EoE.
• Latent variable IDR models are suitable for analyzing bounded, discrete longitudinal endpoints in E-R analyses.