Population-Based Pharmacodynamic Modeling of Omalizumab in Pediatric Patients with Moderate to Severe Persistent...

Omalizumab is the first approved anti-immunoglobulin E (IgE) agent for the treatment of moderate to severe persistent inadequately controlled allergic asthma in adults and adolescents (≥ 12 years old). In 2016, it was approved in pediatric patients (6-11 years old). The objective of this study was to quantitatively characterize the relationship between serum free IgE and pulmonary function (as measured by forced expiratory volume in 1 s [FEV1]) in pediatrics using a population-based pharmacodynamic model. Data collected during the steroid-stable period (first 24 weeks) of an omalizumab trial with pediatric asthma patients (Study IA05) were used to build the pediatric IgE-FEV1 model. The previously developed population IgE-FEV1 model in adults/adolescents was adapted to characterize the FEV1 and IgE relationship in pediatrics with different magnitude and onset of response. The pediatric IgE-FEV1 model adequately characterized the IgE-FEV1 relationship in pediatrics, particularly at the extremes of the observed body weights (i.e., ≤ 30 kg) and IgE values at screening (i.e., > 700 IU/mL). The estimated sigmoidal free IgE-FEV1 curves were similar in shape and maximum effect, but the estimated free IgE concentration leading to 50% maximum effect (IC50) in pediatric patients (39.4, 95% confidence interval [CI] 24.3-63.9 ng/mL) was higher than estimated in adults (19.8, 95% CI 15.1-24.5 ng/mL). The model further confirmed that the current omalizumab dosing rationale based on the mean target free IgE level of 25 ng/ml was appropriate. The pediatric model can be used to predict population FEV1 response for omalizumab when combined with an omalizumab pharmacokinetic-IgE model.