Population Pharmacokinetics and Exposure-Response Analysis of Benralizumab in Chinese Adults, Adolescents, and Pediatric Participants with Severe Eosinophilic Asthma.

INTRODUCTION

Benralizumab is approved as add-on subcutaneous therapy in patients aged ≥ 12 years with severe eosinophilic asthma in > 80 countries, including mainland China.

OBJECTIVE

The study objective was to update benralizumab population pharmacokinetic (popPK) and exposure-response (ER) models in Chinese, Asian (including Chinese), and non-Asian participants.

METHODS

Benralizumab popPK/ER models for asthma exacerbation rate and pre-bronchodilator forced expiratory volume in 1 second (FEV1) were updated for three benralizumab trials involving Chinese, Asian (including Chinese), and non-Asian participants. The ER analysis examined correlations between pharmacokinetic quartiles and annual asthma exacerbation rate (AAER) ratios with simulations comparing predicted clinical outcomes.

RESULTS

Updated data included 17,465 benralizumab concentrations (n = 2855). The updated model predicted a slight, and not clinically relevant, increase (< 14%) in benralizumab exposure for Chinese versus non-Asian adults. Median exposure increased in Chinese adolescents versus adults owing to body weight differences, but no dose adjustment was needed. Chinese children weighing < 35 kg receiving a 10 mg dose had similar exposure to those weighing ≥ 35 kg receiving a 30 mg dose. In Chinese versus non-Chinese participants, there was no trend concerning AAER ratios across different trough concentration quartiles; the maximal treatment effect significantly increased (+127%; p < 0.001), and there was no statistically significant effect on pre-bronchodilator FEV1. Steady-state simulations showed lower predicted AAER ratios in Chinese (0.38; 95% confidence interval [CI] 0.32-0.45) than in non-Chinese adults (0.64; 95% CI 0.60-0.71), and no relevant differences between Chinese adults (0.46; 95% CI 0.38-0.54) and adolescents (0.46; 95% CI 0.37-0.55).

CONCLUSION

The benralizumab popPK/ER models showed good predictive performance across Chinese demographics.

TRIAL REGISTRATION NUMBER: NCT03186209.

TRIAL REGISTRATION DATE: 6 July 2017.