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

被引：93

作者：

Dam, Tien ^{[1
]}

Boxer, Adam L. ^{[2
]}

Golbe, Lawrence, I ^{[3
]}

Hoeglinger, Gunter U. ^{[4
,5
,6
]}

Morris, Huw R. ^{[7
]}

Litvan, Irene ^{[8
]}

Lang, Anthony E. ^{[9
,10
,11
]}

Corvol, Jean-Christophe ^{[12
]}

Aiba, Ikuko ^{[13
]}

Grundman, Michael ^{[8
,14
]}

Yang, Lili ^{[1
]}

Tidemann-Miller, Beth ^{[1
]}

Kupferman, Joseph ^{[1
]}

Harper, Kristine ^{[1
]}

Kamisoglu, Kubra ^{[1
]}

Wald, Michael J. ^{[1
]}

Graham, Danielle L. ^{[1
]}

Gedney, Liz ^{[1
]}

O'Gorman, John ^{[1
]}

Haeberlein, Samantha Budd ^{[1
]}

机构：

[1] Biogen Inc, 14 Cambridge Ctr, Cambridge, MA 02142 USA

[2] Univ Calif San Francisco, Memory & Aging Ctr, Dept Neurol, San Francisco, CA 94143 USA

[3] Rutgers Robert Wood Johnson Med Sch, New Brunswick, NJ USA

[4] Tech Univ Munich, Dept Neurol, Munich, Germany

[5] German Ctr Neurodegenerat Dis, Munich, Germany

[6] Hannover Med Sch, Dept Neurol, Hannover, Germany

[7] Natl Hosp Neurol & Neurosurg, London, England

[8] Univ Calif San Diego, Parkinson & Other Movement Disorders Ctr, San Diego, CA 92103 USA

[9] Edmond J Safra Program Parkinsons Dis, Toronto, ON, Canada

[10] Toronto Western Hosp, Rossy PSP Ctr, Toronto, ON, Canada

[11] Univ Toronto, Toronto, ON, Canada

[12] Sorbonne Univ, Assistance Publ Hop Paris, INSERM, CNRS,Inst Cerveau,Paris Brain Inst ICM,Hop Pitie, Paris, France

[13] Natl Hosp Org, Dept Neurol, Higashinagoya Natl Hosp, Nagoya, Aichi, Japan

[14] Global R&D Partners LLC, San Diego, CA USA

来源：

NATURE MEDICINE | 2021年 / 27卷 / 08期

基金：

英国医学研究理事会; 美国国家卫生研究院;

关键词：

QUALITY-OF-LIFE; DIAGNOSTIC-CRITERIA; EXTRACELLULAR TAU; NEUROPATHOLOGY; BIOMARKERS; DISORDERS; VARIANTS; DISEASE; PSP;

D O I：

10.1038/s41591-021-01455-x

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

In the phase 2 PASSPORT study, treatment with the anti-tau antibody gosuranemab did not show clinical benefit in participants with supranuclear palsy, suggesting that N-terminal tau neutralization does not translate into clinical efficacy. 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, 486 participants 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 week 52 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.

引用

页码：1451 / +

页数：14

共 64 条

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