Honig Lawrence S, Barakos Jerome, Dhadda Shobha, Kanekiyo Michio, Reyderman Larisa, Irizarry Michael, Kramer Lynn D, Swanson Chad J, Sabbagh Marwan
Department of Neurology and Taub Institute for Research on Alzheimer's Disease and the Aging Brain Columbia University Irving Medical Center New York New York USA.
California Pacific Medical Center San Francisco California USA.
Alzheimers Dement (N Y). 2023 Mar 20;9(1):e12377. doi: 10.1002/trc2.12377. eCollection 2023 Jan-Mar.
Lecanemab is a humanized immunoglobulin G1 (IgG1) monoclonal antibody that preferentially targets soluble aggregated Aβ species (protofibrils) with activity at amyloid plaques. Amyloid-related imaging abnormalities (ARIA) profiles appear to differ for various anti-amyloid antibodies. Here, we present ARIA data from a large phase 2 lecanemab trial (Study 201) in early Alzheimer's disease.
Study 201 trial was double-blind, placebo-controlled (core) with an open-label extension (OLE). Observed ARIA events were summarized and modeled via Kaplan-Meier graphs. An exposure response model was developed.
In the phase 2 core and OLE, there was a low incidence of ARIA-E (<10%), with <3% symptomatic cases. ARIA-E was generally asymptomatic, mild-to-moderate in severity, and occurred early (<3 months). ARIA-E was correlated with maximum lecanemab serum concentration and incidence was higher in apolipoprotein E4 (ApoE4) homozygous carriers. ARIA-H and ARIA-E occurred with similar frequency in core and OLE.
Lecanemab can be administered without titration with modest incidence of ARIA.
莱卡奈单抗是一种人源化免疫球蛋白G1（IgG1）单克隆抗体，它优先靶向可溶性聚集的淀粉样蛋白β物种（原纤维），并对淀粉样斑块具有活性。各种抗淀粉样蛋白抗体的淀粉样蛋白相关成像异常（ARIA）特征似乎有所不同。在此，我们展示了一项针对早期阿尔茨海默病的大型2期莱卡奈单抗试验（研究201）的ARIA数据。
研究201试验为双盲、安慰剂对照（核心）试验，并设有开放标签扩展（OLE）。通过Kaplan-Meier图对观察到的ARIA事件进行总结和建模。建立了暴露反应模型。
在2期核心试验和OLE中，ARIA-E的发生率较低（<10%），有症状的病例<3%。ARIA-E通常无症状，严重程度为轻度至中度，且发生较早（<3个月）。ARIA-E与莱卡奈单抗血清最高浓度相关，在载脂蛋白E4（ApoE4）纯合携带者中的发生率更高。ARIA-H和ARIA-E在核心试验和OLE中的发生频率相似。
莱卡奈单抗无需滴定即可给药，ARIA的发生率适中。
