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

Autor: Dam T; Biogen, Cambridge, MA, USA. tien.dam@biogen.com., Boxer AL; Memory and Aging Center, Department of Neurology, University of California, San Francisco, CA, USA., Golbe LI; Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA., Höglinger GU; Department of Neurology, Technische Universität München, Munich, Germany.; German Center for Neurodegenerative Diseases, Munich, Germany.; Department of Neurology, Hanover Medical School, Hanover, Germany., Morris HR; National Hospital for Neurology and Neurosurgery, London, UK., Litvan I; University of California, Parkinson and Other Movement Disorders Center, San Diego, CA, USA., Lang AE; Edmond J. Safra Program in Parkinson's Disease and the Rossy PSP Centre, Toronto Western Hospital and the University of Toronto, Toronto, Ontario, Canada., Corvol JC; Sorbonne Université, Assistance Publique Hôpitaux de Paris, INSERM, CNRS, Institut du Cerveau - Paris Brain Institute - ICM, Hôpital Pitié-Salpêtrière, Paris, France., Aiba I; Department of Neurology, National Hospital Organization Higashinagoya National Hospital, Nagoya, Japan., Grundman M; University of California, Parkinson and Other Movement Disorders Center, San Diego, CA, USA.; Global R&D Partners, LLC, San Diego, CA, USA., Yang L; Biogen, Cambridge, MA, USA., Tidemann-Miller B; Biogen, Cambridge, MA, USA., Kupferman J; Biogen, Cambridge, MA, USA., Harper K; Biogen, Cambridge, MA, USA., Kamisoglu K; Biogen, Cambridge, MA, USA., Wald MJ; Biogen, Cambridge, MA, USA., Graham DL; Biogen, Cambridge, MA, USA., Gedney L; Biogen, Cambridge, MA, USA., O'Gorman J; Biogen, Cambridge, MA, USA., Haeberlein SB; Biogen, Cambridge, MA, USA.
Jazyk: angličtina
Zdroj: Nature medicine [Nat Med] 2021 Aug; Vol. 27 (8), pp. 1451-1457. Date of Electronic Publication: 2021 Aug 12.
DOI: 10.1038/s41591-021-01455-x
Abstrakt: 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.
(© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)
Databáze: MEDLINE
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