Model-informed Drug Development (MIDD) Approach to Support Biopharmaceutical Development of Iberdomide

Area of Science:

• Pharmacokinetics and Drug Development
• Oncology Therapeutics
• Formulation Science

Background:

• Iberdomide is a BCS III CELMoD™ agent for multiple myeloma.
• Five formulations were utilized during clinical development.
• Previous studies indicated no food effect for early formulations.

Purpose of the Study:

• To demonstrate the lack of a food effect for all iberdomide formulations, including the intended commercial form (ICF).
• To bridge clinical data gaps using modeling and simulation.
• To support regulatory submission for the ICF.

Main Methods:

• Utilized a population pharmacokinetic (PK) model to assess formulation impact.
• Employed physiologically-based pharmacokinetic (PBPK) modeling informed by in vitro dissolution data.
• Conducted sensitivity analysis on key pharmacokinetic parameters.

Main Results:

• Population PK modeling confirmed formulation is not a covariate on iberdomide PK.
• PBPK modeling, integrating in vitro dissolution, demonstrated no food effect across all five formulations.
• Sensitivity analysis identified drug release and permeability as critical factors, aligning with BCS III classification.

Conclusions:

• The totality of evidence supports no expected food effect for the intended commercial iberdomide formulation (ICF).
• Modeling and simulation effectively bridged clinical data gaps.
• Iberdomide's absorption is primarily governed by drug release, consistent with its BCS III properties.