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@ARTICLE{Dam:162743,
author = {Dam, Tien and Boxer, Adam L and Golbe, Lawrence I and
Höglinger, Günter and Morris, Huw R and Litvan, Irene and
Lang, Anthony E and Corvol, Jean-Christophe and Aiba, Ikuko
and Grundman, Michael and Yang, Lili and Tidemann-Miller,
Beth and Kupferman, Joseph and Harper, Kristine and
Kamisoglu, Kubra and Wald, Michael J and Graham, Danielle L
and Gedney, Liz and O'Gorman, John and Haeberlein, Samantha
Budd},
collaboration = {Group, PASSPORT Study},
title = {{S}afety and efficacy of anti-tau monoclonal antibody
gosuranemab in progressive supranuclear palsy: a phase 2,
randomized, placebo-controlled trial.},
journal = {Nature medicine},
volume = {27},
number = {8},
issn = {1546-170X},
address = {New York, NY},
publisher = {Nature America Inc.},
reportid = {DZNE-2021-01399},
pages = {1451 - 1457},
year = {2021},
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, 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.},
keywords = {Aged / Antibodies, Monoclonal, Humanized: adverse effects /
Antibodies, Monoclonal, Humanized: therapeutic use /
Double-Blind Method / Female / Humans / Male / Pneumonia:
etiology / Supranuclear Palsy, Progressive: drug therapy /
Treatment Outcome / tau Proteins: immunology / Antibodies,
Monoclonal, Humanized (NLM Chemicals) / MAPT protein, human
(NLM Chemicals) / tau Proteins (NLM Chemicals) / gosuranemab
(NLM Chemicals)},
cin = {Clinical Research (Munich)},
ddc = {610},
cid = {I:(DE-2719)1111015},
pnm = {353 - Clinical and Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-353},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:34385707},
doi = {10.1038/s41591-021-01455-x},
url = {https://pub.dzne.de/record/162743},
}