Iberdomide Biopharmaceutical Risk Assessment Using Model Informed Drug Development Approach

Iberdomide is a BCS III drug where systemic exposure is limited by dissolution rate and permeability of the molecule, but not solubility. During development, multiple stage-appropriate formulations were developed for clinical evaluation, ranging from active in capsule (AIC) for Phase 1 to formulated capsule as intended commercial formulation (ICF). Formulations were bridged through relative bioavailability studies. A food-effect study with Phase 1 AIC showed no food effect. Team leveraged model informed drug development approach (biorelevant dissolution-based PBPK modeling) to predict no food-effect with ICF. Sensitivity analysis using the PBPK model demonstrated that permeability and total amount of drug released from formulation are the most sensitive parameters in defining the systemic exposure of iberdomide, in agreement with iberdomide’s BCS III classification. The approach demonstrates how clinical data (real-world data) can be combined with modeling and simulation to explore untested scenarios with reasonable confidence without carrying additional resource intensive clinical studies.