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Straight to Phase III: Model-Informed Approach Speeds Depemokimab Clinical Development in Interleukin-5-Driven
Chiara Zecchin1, Stein Schalkwijk2, Isabelle J Pouliquen3
1Clinical Pharmacology Modelling and Simulation, GSK, Stevenage, UK.
Clinical Pharmacology and Therapeutics
|January 20, 2026
Summary
Model-informed drug development (MIDD) and quantitative decision making (QDM) accelerated depemokimab
Area of Science:
- Pharmacometrics and clinical pharmacology
- Biologics and therapeutic development
- Inflammatory disease research
Background:
- Interleukin-5 (IL-5) drives type 2 inflammation in severe asthma, CRSwNP, EGPA, and HES.
- Blood eosinophil count (BEC) reduction is a key biomarker for anti-IL-5 biologic efficacy.
- Depemokimab is an ultra-long-acting anti-IL-5 biologic therapy.
Purpose of the Study:
- To utilize model-informed drug development (MIDD) and quantitative decision making (QDM) to optimize depemokimab clinical development.
- To predict effective depemokimab dosing for severe asthma, CRSwNP, EGPA, and HES based on BEC reduction.
- To assess the efficiency of MIDD/QDM in accelerating the progression of depemokimab to Phase III trials.
Main Methods:
- Developed a Bayesian nonlinear mixed-effects dose-time response model to predict depemokimab dose for comparable BEC reduction to mepolizumab.
- Employed quantitative decision making (QDM) with prespecified go/no-go criteria to evaluate success probability.
- Conducted Phase IIb trial simulations using negative binomial distribution for annualized exacerbation rates and a PK/PD (BEC) model for Phase III dose prediction.
Main Results:
- A single depemokimab dose ≥60 mg demonstrated ≥80% probability of exceeding minimum BEC reduction targets observed in Phase III trials.
- Clinical trial simulations indicated <3% probability of improving Phase III dose precision with conventional dose-ranging studies.
- Selected depemokimab doses: 100 mg for severe asthma/CRSwNP and 200 mg for EGPA/HES, every 26 weeks for Phase III.
Conclusions:
- MIDD and QDM successfully predicted optimal depemokimab Phase III doses, achieving target BEC reductions.
- The MIDD/QDM approach significantly shortened the depemokimab development timeline by 2-3 years.
- This strategy highlights the potential for advancing novel therapies directly from Phase I to Phase III, optimizing drug development efficiency.
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