美国Biogen公司Tien Dam等研究人员完成抗tau单克隆抗体gosuranemab对进行性核上性麻痹的安全性和有效性的临床试验。相关论文于2021年8月12日在线发表在《自然—医学》杂志上。

一项随机、双盲、安慰剂对照、为期52周的研究（编号：NCT03068468）评估了gosuranemab，一种抗tau单克隆抗体，用于治疗进行性核上麻痹（PSP）。总共有486名参与者被分配到gosuranemab（n=321）或安慰剂（n=165）。在第52周，gosuranemab和安慰剂之间的PSP评分表调整后的平均变化（10.4对10.6，P=0.85，主要终点），或次要终点都没有显示出疗效，导致开放标签的长期扩展项目中止了。

使用gosuranemab后，脑脊液中未结合的N端tau减少了98%，使用安慰剂后增加了11%（P<0.0001）。各组间不良事件和死亡的发生率相似。这项研究表明，N端tau中和并不能转化为临床疗效。

附：英文原文

Title: Safety and efficacy of anti-tau monoclonal antibody gosuranemab in progressive supranuclear palsy: a phase 2, randomized, placebo-controlled trial

Author: Dam, Tien, Boxer, Adam L., Golbe, Lawrence I., Hglinger, Gnter U., Morris, Huw R., Litvan, Irene, Lang, Anthony E., Corvol, Jean-Christophe, Aiba, Ikuko, Grundman, Michael, Yang, Lili, Tidemann-Miller, Beth, Kupferman, Joseph, Harper, Kristine, Kamisoglu, Kubra, Wald, Michael J., Graham, Danielle L., Gedney, Liz, OGorman, John, Haeberlein, Samantha Budd

Issue&Volume: 2021-08-12

Abstract: A randomized, double-blind, placebo-controlled, 52-week study (no. NCT03068468) evaluated gosuranemab, an anti-tau monoclonal antibody, in the treatment of progressive supranuclear palsy (PSP). In total, 486participants dosed were assigned to either gosuranemab (n=321) or placebo (n=165). Efficacy was not demonstrated on adjusted mean change of PSP Rating Scale score at week52 between gosuranemab and placebo (10.4 versus 10.6, P=0.85, primary endpoint), or at secondary endpoints, resulting in discontinuation of the open-label, long-term extension. Unbound N-terminal tau in cerebrospinal fluid decreased by 98% with gosuranemab and increased by 11% with placebo (P<0.0001). Incidences of adverse events and deaths were similar between groups. This well-powered study suggests that N-terminal tau neutralization does not translate into clinical efficacy.

DOI: 10.1038/s41591-021-01455-x

Source: https://www.nature.com/articles/s41591-021-01455-x