Jing Shan, Zhang Yu, Lin Yang, Gu Xiaowen, Liu Jing, Guglietta Antonio, Noukens Jan, Van Bragt Tonke, Wang Lina, Chen Jiajia, Reinhart Harald, Pu Xia
Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Drugs R D. 2024 Dec;24(4):505-515. doi: 10.1007/s40268-024-00490-6. Epub 2024 Oct 5.
Efgartigimod, a human immunoglobulin G (IgG)1-derived Fc fragment targeting the neonatal Fc receptor, has been developed into intravenous (IV) and subcutaneous (SC) formulations for treating generalized myasthenia gravis (gMG) and other autoimmune diseases. Data in the Chinese population were not available to date, and while both formulations have been approved in the USA, the EU, Japan and China for the treatment of gMG.
We present the pharmacokinetic, pharmacodynamic, and safety of IV and SC PH20 efgartigimod in healthy Chinese participants.
In two independent, double-blinded, placebo-controlled, phase I studies of the IV and SC formulations of efgartigimod, healthy Chinese adults were randomized 3:1 to receive active treatment or matching placebo once every 7 days for four doses. Primary endpoints were pharmacokinetic parameters.
After the fourth IV infusion, a mean maximum observed concentration (C) of 194 µg/mL was reached at the end of the 1 h infusion; the mean area under concentration-time curve from time zero to 168 h (AUC) was 5300 µg × h/mL. After the fourth SC injection, a mean C of 42.1 µg/mL was achieved with a median T of 47.74 h; the mean AUC was 4790 µg × h/mL. Maximal mean reductions from baseline in total IgG levels were reached approximately 24 days after the first dose (60.7%, IV formulation; 66.4%, SC formulation). Treatment-related adverse events (TRAEs) were reported in seven (58.3%) participants receiving SC efgartigimod, mostly injection-site reactions. No TRAEs or AEs of special interest were reported in the IV study.
The efgartigimod IV and SC pharmacokinetic, pharmacodynamic, and safety profiles in Chinese participants were similar to the known profiles in non-Chinese participants. Both formulations effectively reduced total IgG levels by a similar percentage.
CTR20211952 and CTR20211805.
艾加莫德是一种靶向新生儿Fc受体的人免疫球蛋白G（IgG）1衍生Fc片段，已开发出静脉注射（IV）和皮下注射（SC）制剂，用于治疗全身型重症肌无力（gMG）和其他自身免疫性疾病。目前尚无中国人群的数据，尽管这两种制剂均已在美国、欧盟、日本和中国获批用于治疗gMG。
我们展示了静脉注射和皮下注射PH20艾加莫德在中国健康受试者中的药代动力学、药效学和安全性。
在两项独立、双盲、安慰剂对照的艾加莫德静脉注射和皮下注射制剂的I期研究中，中国健康成年人按3:1随机分组，每7天接受一次活性治疗或匹配的安慰剂，共给药四剂。主要终点是药代动力学参数。
第四次静脉输注后，在1小时输注结束时达到的平均最大观察浓度（Cmax）为194μg/mL；从零时间到168小时的浓度-时间曲线下面积（AUC）平均值为5300μg·h/mL。第四次皮下注射后，平均Cmax为42.1μg/mL，中位达峰时间（Tmax）为47.74小时；平均AUC为4790μg·h/mL。首次给药后约24天，总IgG水平较基线的最大平均降幅达到（静脉注射制剂为60.7%；皮下注射制剂为66.4%）。接受皮下注射艾加莫德的7名（58.3%）受试者报告了治疗相关不良事件（TRAEs），主要是注射部位反应。静脉注射研究中未报告TRAEs或特别关注的不良事件（AEs）。
中国受试者中艾加莫德静脉注射和皮下注射的药代动力学、药效学和安全性特征与非中国受试者的已知特征相似。两种制剂均能有效降低总IgG水平，降低百分比相似。
CTR20211952和CTR20211805。
