倍利珠单抗在中国患有重度嗜酸性粒细胞性哮喘的成人、青少年和儿童参与者中的群体药代动力学及暴露-反应分析。

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

作者信息

Jin Yuwen, Guiastrennec Benjamin, Stuke Miriam, Yao Yuhui, Zhang Yajuan, Barker Peter, Jison Maria, Penland Robert C, Ding Junjie, Lukka Pradeep B

机构信息

Clinical Pharmacology, R&D China, AstraZeneca, Shanghai, China.

IntiQuan AG, Basel, Switzerland.

出版信息

Clin Pharmacokinet. 2025 Jun 23. doi: 10.1007/s40262-025-01538-9.

DOI:10.1007/s40262-025-01538-9

PMID:40551003

Abstract

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 (FEV) 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 FEV. 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.

摘要

引言

在包括中国大陆在内的80多个国家，贝那利珠单抗被批准作为≥12岁重度嗜酸性粒细胞性哮喘患者的皮下附加治疗药物。

目的

本研究旨在更新中国、亚洲（包括中国）和非亚洲参与者中贝那利珠单抗的群体药代动力学（popPK）和暴露-反应（ER）模型。

方法

针对三项涉及中国、亚洲（包括中国）和非亚洲参与者的贝那利珠单抗试验，更新了用于哮喘加重率和支气管扩张剂使用前1秒用力呼气容积（FEV）的贝那利珠单抗popPK/ER模型。ER分析通过模拟比较预测的临床结局，研究了药代动力学四分位数与年度哮喘加重率（AAER）比值之间的相关性。

结果

更新后的数据包括17465个贝那利珠单抗浓度（n = 2855）。更新后的模型预测，与非亚洲成年人相比，中国成年人的贝那利珠单抗暴露量略有增加（<14%），但无临床相关性。由于体重差异，中国青少年的中位暴露量高于成年人，但无需调整剂量。体重<35 kg的中国儿童接受10 mg剂量时的暴露量与体重≥35 kg接受30 mg剂量的儿童相似。在中国参与者与非中国参与者中，不同谷浓度四分位数的AAER比值无明显趋势；最大治疗效果显著增加（+127%；p<0.001），且对支气管扩张剂使用前FEV无统计学显著影响。稳态模拟显示，中国成年人（0.38；95%置信区间[CI] 0.32 - 0.45）的预测AAER比值低于非中国成年人（0.64；95% CI 0.60 - 0.71），中国成年人（0.46；95% CI 0.38 - 0.54）与青少年（0.46；95% CI 0.37 - 0.55）之间无显著差异。