Population pharmacokinetics and pharmacodynamics of depemokimab in people with asthma and chronic rhinosinusitis with nasal polyps

Type 2 inflammation is a core driver in airway diseases such as severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). While monoclonal antibody therapies have significantly improved patient outcomes, the typical bi-weekly or monthly administration can present a high treatment burden. Depemokimab has now received regulatory approval for both indications.

This research, presented in a new publication by Lénaïg Tanneau, Alexandra Lavalley-Morelle, and Jakob Ribbing from Pharmetheus, in collaboration with Anders Thorsted and colleagues from GSK, Universiteit Gent and University of Oxford, characterizes the pharmacokinetic/pharmacodynamic (PK/PD) profile of depemokimab, the first ultra-long-acting biologic designed to address this challenge through twice-yearly dosing.

Highlights from the population PK/PD modeling:

•  Sustained efficacy: a single 100 mg dose provided durable reduction of blood eosinophil counts (BEC) to <25% of baseline throughout the 26-week dosing interval.
•  Stable exposure: the predicted geometric mean half-life was 47 days, with negligible drug accumulation observed between doses.
•  Robust dosing: all participants maintained trough concentrations above the half maximal effective concentration (EC50) at the end of the dosing interval.
•  Broad application: no clinically relevant covariates were identified, indicating that no dose adjustments are required based on e.g. age, race, or body weight.
• These findings validate the 100 mg twice-yearly regimen, offering a potential path to improved treatment adherence and reduced burden for patients living with type 2-driven airway diseases.

By utilizing a model-informed drug development (MIDD) approach, these analyses bridge the gap between early-phase clinical data and the successful phase III outcomes that support depemokimab as a new standard for long-acting biologic therapy. By connecting a single-dose Phase 1 study directly to the initiation of the four Phase-3 studies included in this analysis, this program highlights how MIDD can optimize and accelerate clinical development timelines.