Jin Yuwen, Guiastrennec Benjamin, Stuke Miriam, Yao Yuhui, Zhang Yajuan, Barker Peter, Jison Maria, Penland Robert C, Ding Junjie, Lukka Pradeep B
Clinical Pharmacology, R&D China, AstraZeneca, Shanghai, China.
IntiQuan AG, Basel, Switzerland.
Clin Pharmacokinet. 2025 Jun 23. doi: 10.1007/s40262-025-01538-9.
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 (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.
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).
The benralizumab popPK/ER models showed good predictive performance across Chinese demographics.
NCT03186209.
6 July 2017.
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。
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。
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。
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。
贝那利珠单抗popPK/ER模型在中国不同人群中显示出良好的预测性能。
NCT03186209。
2017年7月6日。
