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

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

  • Nat Med. 2021 Aug;27(8):1451-1457. doi: 10.1038/s41591-021-01455-x.
Tien Dam 1 Adam L Boxer 2 Lawrence I Golbe 3 Günter U Höglinger 4 5 6 Huw R Morris 7 Irene Litvan 8 Anthony E Lang 9 Jean-Christophe Corvol 10 Ikuko Aiba 11 Michael Grundman 8 12 Lili Yang 13 Beth Tidemann-Miller 13 Joseph Kupferman 13 Kristine Harper 13 Kubra Kamisoglu 13 Michael J Wald 13 Danielle L Graham 13 Liz Gedney 13 John O'Gorman 13 Samantha Budd Haeberlein 13 PASSPORT Study Group
Affiliations

Affiliations

  • 1 Biogen, Cambridge, MA, USA. tien.dam@biogen.com.
  • 2 Memory and Aging Center, Department of Neurology, University of California, San Francisco, CA, USA.
  • 3 Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA.
  • 4 Department of Neurology, Technische Universität München, Munich, Germany.
  • 5 German Center for Neurodegenerative Diseases, Munich, Germany.
  • 6 Department of Neurology, Hanover Medical School, Hanover, Germany.
  • 7 National Hospital for Neurology and Neurosurgery, London, UK.
  • 8 University of California, Parkinson and Other Movement Disorders Center, San Diego, CA, USA.
  • 9 Edmond J. Safra Program in Parkinson's Disease and the Rossy PSP Centre, Toronto Western Hospital and the University of Toronto, Toronto, Ontario, Canada.
  • 10 Sorbonne Université, Assistance Publique Hôpitaux de Paris, INSERM, CNRS, Institut du Cerveau - Paris Brain Institute - ICM, Hôpital Pitié-Salpêtrière, Paris, France.
  • 11 Department of Neurology, National Hospital Organization Higashinagoya National Hospital, Nagoya, Japan.
  • 12 Global R&D Partners, LLC, San Diego, CA, USA.
  • 13 Biogen, Cambridge, MA, USA.
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.

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