Momenta Pharmaceuticals, Inc., Cambridge, Massachusetts, USA.
PRA Health Sciences, Groningen, The Netherlands.
Clin Pharmacol Ther. 2019 Apr;105(4):1031-1039. doi: 10.1002/cpt.1276. Epub 2018 Dec 4.
M281 is a fully human, anti-neonatal Fc receptor (FcRn) antibody that inhibits FcRn-mediated immunoglobulin G (IgG) recycling to decrease pathogenic IgG while preserving IgG production. A randomized, double-blind, placebo-controlled, first-in-human study with 50 normal healthy volunteers was designed to probe safety and the physiological maximum for reduction of IgG. Intravenous infusion of single ascending doses up to 60 mg/kg induced dose-dependent serum IgG reductions, which were similar across all IgG subclasses. Multiple weekly doses of 15 or 30 mg/kg achieved mean IgG reductions of ≈85% from baseline and maintained IgG reductions ≥75% from baseline for up to 24 days. M281 was well tolerated, with no serious or severe adverse events (AEs), few moderate AEs, and a low incidence of infection-related AEs similar to placebo treatment. The tolerability and consistency of M281 pharmacokinetics and pharmacodynamics support further evaluation of M281 in diseases mediated by pathogenic IgG.
M281 是一种全人源抗新生 Fc 受体（FcRn）抗体，可抑制 FcRn 介导的免疫球蛋白 G（IgG）再循环，从而减少致病性 IgG，同时保留 IgG 的产生。一项设计用于探究安全性和 IgG 降低的生理上限的、在 50 名健康志愿者中开展的、随机、双盲、安慰剂对照的首次人体研究显示，单次递增剂量静脉输注高达 60mg/kg 可诱导剂量依赖性的血清 IgG 降低，且所有 IgG 亚类的降低幅度相似。每周多次输注 15 或 30mg/kg，可使 IgG 基线降低约 85%，且 IgG 降低可持续至 24 天，≥75%的基线水平。M281 具有良好的耐受性，无严重或严重不良事件（AE），仅有少数中度 AE，且感染相关 AE 的发生率与安慰剂治疗相似。M281 的药代动力学和药效学具有良好的耐受性和一致性，支持其在致病性 IgG 介导的疾病中进一步评估。
