PII-085 - POPULATION-BASED EFFICACY MODELING OF OMALIZUMAB IN PEDIATRIC PATIENTS WITH MODERATE TO SEVERE PERSISTENT INADEQUATELY CONTROLLED ALLERGIC ASTHMA.

R. Zhu¹, X. Wang², M. Deng¹, S. Pivirotto¹, J. JIn¹, N. Kassir¹, R. Owen¹; ¹Genentech, South San Francisco, CA, USA, ²Metrum Research Group, Tariffville, CT, USA.

Background: Omalizumab is the first FDA approved anti-immunoglobulin E (IgE) agent for the treatment of moderate to severe inadequately controlled allergic asthma in adults and adolescents (≥12 years old) (2003). In 2016, FDA approved it in pediatrics (6-11 years old). The objective of this study was to characterize relationship between serum free IgE and pulmonary function (as measured by forced expiratory volume in 1 s [FEV1]) in pediatrics using population-based efficacy model.

Methods: A population IgE-FEV1 model was previously developed in adults/adolescents [1]. This model was adapted to characterize the FEV1 and IgE relationship in pediatrics with a different response (e.g., alternative structural models, random effects structures and covariate models were tested) using data collected during the steroid-stable period (week 0-24) of Study IA05. Model was evaluated with goodness-of-fit criteria and visual predictive checks.

Results: The analysis used a total of 1515 FEV1 samples from 535 pediatric patients. The pediatric IgE-FEV1 model was able to adequately describe the pediatric data and also to characterize the IgE-FEV1 relationship at the extremes of the observed bodyweights (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. The estimated IC50 in pediatric patients (39.4, 95% CI 24.3-63.9 ng/mL) was slightly higher than that estimated in adults (19.8, 95% CI 15.1-24.5 ng/mL) [1].

Conclusion: The efficacy model further confirmed the current omalizumab dosing rationale based on the mean target free IgE level of 25 ng/ml and quantified the variability for the target. The pediatric model could be used to predict population FEV1 response for omalizumab when combined with the PK-IgE model.

Rui Zhu, Yanan Zheng, Wendy S. Putnam, Jennifer Visich, Mark D. Eisner, John G. Matthews, Karin E. Rosen, and David Z. D’Argenio. Population-Based Efficacy Modeling of Omalizumab in Patients with Severe Allergic Asthma Inadequately Controlled with Standard Therapy. AAPS J. 2013 Apr; 15(2): 559–570.