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

Benralizumab is approved as add-on subcutaneous therapy in patients aged ≥ 12 years with severe eosinophilic asthma in > 80 countries, including mainland China. The study objective was to update benralizumab population pharmacokinetic (popPK) and exposure–response (ER) models in Chinese, Asian (including Chinese), and non-Asian participants. 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. 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). The benralizumab popPK/ER models showed good predictive performance across Chinese demographics. NCT03186209. 6 July 2017. Benralizumab is a medicine used to treat people aged 12 years or over with severe eosinophilic asthma, a type of asthma with elevated levels of white blood cells (eosinophils). The drug is approved in over 80 countries, including mainland China. In this study, researchers used a mathematical model to describe concentrations of benralizumab in the human body and how this relates to the number of asthma attacks (exacerbations) each year and lung function (measured as forced expiratory volume in 1 second). The researchers added new data from three studies that included Chinese and other Asian participants. Findings showed that benralizumab worked similarly well in Chinese and non-Asian adults and that there was no need to change the dose for teenagers (adolescents). The medicine shows signs of working better in Chinese adults than in non-Chinese adults, based on fewer asthma attacks. There were no direct data for younger Chinese children, and predictions were made using an exposure–response model (which helps select the appropriate dose of a drug) based on data from non-Chinese adolescents and the single Chinese adolescent. These results are important because they help doctors understand that benralizumab will work well at a dose of 10 mg for children who weigh less than 35 kg and at a dose of 30 mg for everyone else, including Chinese adults, teenagers, and other children with severe eosinophilic asthma.