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
  • 1. Biogen, Cambridge, MA, USA. [email protected].
  • 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.
PMID: 34385707 DOI: 10.1038/s41591-021-01455-x
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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