Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

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

Nature Medicine volume 27, pages 1451–1457 (2021)Cite this article

Subjects

An Author Correction to this article was published on 17 October 2022

This article has been updated

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.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Change from baseline in total PSPRS over 52 weeks (ITT population).

Similar content being viewed by others

Data availability

To request access to data, please visit http://www.biogenclinicaldatarequest.com. The individual participant data collected during the trial and that support the research proposal will be available to qualified scientific researchers after anonymization and following approval of the research proposal. Anonymization of the datasets is necessary to allow sharing of data ethically and legally, and to maximize their significant social, environmental and economic value while preserving the confidentiality of the individuals who participated in studies conducted by Biogen. An initial status update of the request will take approximately two (2) business days after the request’s submission date. The requester will be notified of the outcome of the request in approximately thirty (30) business days. Source data are provided with this paper.

Change history

References

  1. Boxer, A. L. et al. Advances in progressive supranuclear palsy: new diagnostic criteria, biomarkers, and therapeutic approaches. Lancet Neurol. 16, 552–563 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  2. Höglinger, G. U. et al. Clinical diagnosis of progressive supranuclear palsy: the movement disorder society criteria. Mov. Disord. 32, 853–864 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  3. Picillo, M. et al. Motor, cognitive and behavioral differences in MDS PSP phenotypes. J. Neurol. 266, 1727–1735 (2019).

    Article  PubMed  Google Scholar 

  4. Golbe, L. I. Progressive supranuclear palsy. Semin. Neurol. 34, 151–159 (2014).

    Article  PubMed  Google Scholar 

  5. Litvan, I. et al. Clinical research criteria for the diagnosis of progressive supranuclear palsy (Steele–Richardson–Olszewski syndrome): report of the NINDS-SPSP international workshop. Neurology 47, 1–9 (1996).

    Article  CAS  PubMed  Google Scholar 

  6. Golbe, L. I. & Ohman-Strickland, P. A. A clinical rating scale for progressive supranuclear palsy. Brain 130, 1552–1565 (2007).

    Article  PubMed  Google Scholar 

  7. Respondek, G. et al. Accuracy of the National Institute for Neurological Disorders and Stroke/Society for Progressive Supranuclear Palsy and neuroprotection and natural history in Parkinson plus syndromes criteria for the diagnosis of progressive supranuclear palsy. Mov. Disord. 28, 504–509 (2013).

    Article  PubMed  Google Scholar 

  8. Dickson, D. W., Ahmed, Z., Algom, A. A., Tsuboi, Y. & Josephs, K. A. Neuropathology of variants of progressive supranuclear palsy. Curr. Opin. Neurol. 23, 394–400 (2010).

    Article  PubMed  Google Scholar 

  9. Dickson, D. W. Parkinson’s disease and parkinsonism: neuropathology. Cold Spring Harb. Perspect. Med. 2, a009258 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  10. Fuster-Matanzo, A., Hernández, F. & Ávila, J. Tau spreading mechanisms; implications for dysfunctional tauopathies. Int. J. Mol. Sci. 19, 645 (2018).

    Article  PubMed Central  Google Scholar 

  11. Meredith, J. E. Jr. et al. Characterization of novel CSF tau and ptau biomarkers for Alzheimer’s disease. PLoS One 8, e76523 (2013).

    Article  CAS  PubMed  Google Scholar 

  12. Bright, J. et al. Human secreted tau increases amyloid-beta production. Neurobiol. Aging 36, 693–709 (2015).

    Article  CAS  PubMed  Google Scholar 

  13. Sato, C. et al. Tau kinetics in neurons and the human central nervous system. Neuron 97, 1284–1298 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Clavaguera, F. et al. Brain homogenates from human tauopathies induce tau inclusions in mouse brain. Proc. Natl Acad. Sci. USA 110, 9535–9540 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Mocanu, M. M. et al. The potential for beta-structure in the repeat domain of tau protein determines aggregation, synaptic decay, neuronal loss, and coassembly with endogenous tau in inducible mouse models of tauopathy. J. Neurosci. 28, 737–748 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Sanders, D. W. et al. Distinct tau prion strains propagate in cells and mice and define different tauopathies. Neuron 82, 1271–1288 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Golonzhka, O. et al. Functional characterization of anti-tau monoclonal antibody BIIB092. Presented at 14th International Conference on Alzheimer’s and Parkinson’s Diseases (26–31 March, 2019, Lisbon, Portugal).

  18. Czerkowicz, J. et al. Pharmacokinetic and target engagement analysis of anti-tau antibody gosuranemab [BIIB092] in cynomolgus monkey central nervous system fluid compartments. Alzheimers Dement. 15, 1288–1289 (2019).

    Article  Google Scholar 

  19. Qureshi, I. A. et al. A randomized, single ascending dose study of intravenous BIIB092 in healthy participants. Alzheimers Dement. 4, 746–755 (2018).

    Article  Google Scholar 

  20. Boxer, A. L. et al. Safety of the tau-directed monoclonal antibody BIIB092 in progressive supranuclear palsy: a randomised, placebo-controlled, multiple ascending dose phase 1b trial. Lancet Neurol. 18, 549–558 (2019).

    Article  CAS  PubMed  Google Scholar 

  21. Boxer, A. L. et al. Davunetide in patients with progressive supranuclear palsy: a randomised, double-blind, placebo-controlled phase 2/3 trial. Lancet Neurol. 13, 676–685 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Papapetropoulos, S., Singer, C., McCorquodale, D., Gonzalez, J. & Mash, D. C. Cause, seasonality of death and co-morbidities in progressive supranuclear palsy (PSP). Parkinsonism Relat. Disord. 11, 459–463 (2005).

    Article  PubMed  Google Scholar 

  23. Höglinger, G. U. et al. Longitudinal magnetic resonance imaging in progressive supranuclear palsy: a new combined score for clinical trials. Mov. Disord. 32, 842–852 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  24. Whitwell, J. L. et al. Radiological biomarkers for diagnosis in PSP: where are we and where do we need to be? Mov. Disord. 32, 955–971 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  25. Josephs, K. A. et al. Modeling trajectories of regional volume loss in progressive supranuclear palsy. Mov. Disord. 28, 1117–1124 (2013).

    Article  PubMed  Google Scholar 

  26. Tsai, R. M. et al. Clinical correlates of longitudinal brain atrophy in progressive supranuclear palsy. Parkinsonism Relat. Disord. 28, 29–35 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  27. Tolosa, E. et al. A phase 2 trial of the GSK-3 inhibitor tideglusib in progressive supranuclear palsy. Mov. Disord. 29, 470–478 (2014).

    Article  CAS  PubMed  Google Scholar 

  28. Doble, A. The pharmacology and mechanism of action of riluzole. Neurology 47, S233–S241 (1996).

    Article  CAS  PubMed  Google Scholar 

  29. Bensimon, G. et al. Riluzole treatment, survival and diagnostic criteria in Parkinson plus disorders: the NNIPPS study. Brain 132, 156–171 (2009).

    Article  PubMed  Google Scholar 

  30. Vaswani, P. A. & Olsen, A. L. Immunotherapy in progressive supranuclear palsy. Curr. Opin. Neurol. 33, 527–533 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  31. Schrag, A. et al. Measuring quality of life in PSP: the PSP-QoL. Neurology 67, 39–44 (2006).

    Article  CAS  PubMed  Google Scholar 

  32. Goetz, C. G. et al. Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS): scale presentation and clinimetric testing results. Mov. Disord. 23, 2129–2170 (2008).

    Article  PubMed  Google Scholar 

  33. Shoeibi, A. et al. Are the International Parkinson disease and Movement Disorder Society progressive supranuclear palsy (IPMDS-PSP) diagnostic criteria accurate enough to differentiate common PSP phenotypes? Parkinsonism Relat. Disord. 69, 34–39 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  34. Respondek, G. et al. The phenotypic spectrum of progressive supranuclear palsy: a retrospective multicenter study of 100 definite cases. Mov. Disord. 29, 1758–1766 (2014).

    Article  PubMed  Google Scholar 

  35. Martínez-Martín, P. et al. Parkinson’s disease severity levels and MDS-Unified Parkinson’s Disease Rating Scale. Parkinsonism Relat. Disord. 21, 50–54 (2015).

    Article  PubMed  Google Scholar 

  36. Busner, J. & Targum, S. D. The clinical global impressions scale: applying a research tool in clinical practice. Psychiatry 4, 28–37 (2007).

    PubMed  PubMed Central  Google Scholar 

  37. Mamarabadi, M., Razjouyan, H. & Golbe, L. I. Is the latency from progressive supranuclear palsy onset to diagnosis improving? Mov. Disord. Clin. Pract. 5, 603–606 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  38. Armstrong, R. A. Visual signs and symptoms of progressive supranuclear palsy. Clin. Exp. Optom. 94, 150–160 (2011).

    Article  PubMed  Google Scholar 

  39. Respondek, G. et al. Which ante mortem clinical features predict progressive supranuclear palsy pathology? Mov. Disord. 32, 995–1005 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  40. Ali, F. et al. Sensitivity and specificity of diagnostic criteria for progressive supranuclear palsy. Mov. Disord. 34, 1144–1153 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  41. Höglinger, G. U. et al. Identification of common variants influencing risk of the tauopathy progressive supranuclear palsy. Nat. Genet. 43, 699–705 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  42. Sopko, R. et al. Characterization of tau binding by gosuranemab. Neurobiol. Dis. 146, 105120 (2020).

    Article  CAS  PubMed  Google Scholar 

  43. Bright, J. et al. Human secreted tau increases amyloid-beta production. Neurobiol. Aging 36, 693–709 (2015).

    Article  CAS  PubMed  Google Scholar 

  44. Gómez-Ramos, A., Díaz-Hernández, M., Cuadros, R., Hernández, F. & Avila, J. Extracellular tau is toxic to neuronal cells. FEBS Lett. 580, 4842–4850 (2006).

    Article  PubMed  Google Scholar 

  45. Gómez-Ramos, A., Díaz-Hernández, M., Rubio, A., Miras-Portugal, M. T. & Avila, J. Extracellular tau promotes intracellular calcium increase through M1 and M3 muscarinic receptors in neuronal cells. Mol. Cell. Neurosci. 37, 673–681 (2008).

    Article  PubMed  Google Scholar 

  46. Gibbons, G. S., Lee, V. M. Y. & Trojanowski, J. Q. Mechanisms of cell-to-cell transmission of pathological tau: a review. JAMA Neurol. 76, 101–108 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  47. Yamada, K. Extracellular tau and its potential role in the propagation of tau pathology. Front. Neurosci. 11, 667 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  48. Courade, J. P. et al. Epitope determines efficacy of therapeutic anti-tau antibodies in a functional assay with human Alzheimer tau. Acta Neuropathol. 136, 729–745 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Guo, J. L. et al. Unique pathological tau conformers from Alzheimer’s brains transmit tau pathology in nontransgenic mice. J. Exp. Med. 213, 2635–2654 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Czerkowicz, J. et al. Anti-tau antibody BIIB092 binds secreted tau in preclinical models and Alzheimer’s disease cerebrospinal fluid. Alzheimers Dement. 14, P1441 (2018); https://alz-journals.onlinelibrary.wiley.com/doi/10.1016/j.jalz.2018.06.2423

  51. Scheres, S. H., Zhang, W., Falcon, B. & Goedert, M. Cryo-EM structures of tau filaments. Curr. Opin. Struct. Biol. 64, 17–25 (2020).

    Article  CAS  PubMed  Google Scholar 

  52. Höglinger, G. U. et al. Safety and efficacy of tilavonemab in progressive supranuclear palsy: a phase 2, randomised, placebo-controlled trial. Lancet Neurol. 20, 182–192 (2021).

    Article  PubMed  Google Scholar 

  53. Hall, S. et al. Cerebrospinal fluid concentrations of inflammatory markers in Parkinson’s disease and atypical parkinsonian disorders. Sci. Rep. 8, 13276 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  54. Hall, S. et al. Accuracy of a panel of 5 cerebrospinal fluid biomarkers in the differential diagnosis of patients with dementia and/or parkinsonian disorders. Arch. Neurol. 69, 1445–1452 (2012).

    Article  PubMed  Google Scholar 

  55. Wagshal, D. et al. Divergent CSF τ alterations in two common tauopathies: Alzheimer’s disease and progressive supranuclear palsy. J. Neurol. Neurosurg. Psychiatry 86, 244–250 (2015).

    Article  PubMed  Google Scholar 

  56. Kovacs, G. G. Invited review: neuropathology of tauopathies: principles and practice. Neuropathol. Appl. Neurobiol. 41, 3–23 (2015).

    Article  CAS  PubMed  Google Scholar 

  57. Shoeibi, A., Olfati, N. & Litvan, I. Preclinical, phase I, and phase II investigational clinical trials for treatment of progressive supranuclear palsy. Expert Opin. Investig. Drugs 27, 349–361 (2018).

    Article  CAS  PubMed  Google Scholar 

  58. Grimm, M. J. et al. Movement Disorder Society-Endorsed PSP Study Group. Clinical conditions ‘suggestive of progressive supranuclear palsy’—diagnostic performance. Mov. Disord. https://doi.org/10.1002/mds.28263 (2020).

  59. D’Elia, L. F., Satz, P., Uchiyama, C. L. & White, T. Color Trails Test. Professional Manual (Psychological Assessment Resources, 1996).

  60. Wolz, R., Aljabar, P., Hajnal, J. V., Hammers, A. & Rueckert, D. LEAP: learning embeddings for atlas propagation. Neuroimage 49, 1316–1325 (2010).

    Article  PubMed  Google Scholar 

  61. Guy, W. ECDEU Assessment Manual for Psychopharmacology (US Department of Health, Education, and Welfare, 1976).

  62. Karantzoulis, S., Novitski, J., Gold, M. & Randolph, C. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS): utility in detection and characterization of mild cognitive impairment due to Alzheimer’s disease. Arch. Clin. Neuropsychol. 28, 837–844 (2013).

    Article  PubMed  Google Scholar 

  63. Dal Bello-Haas, V., Klassen, L., Sheppard, M. S. & Metcalfe, A. Psychometric properties of activity, self-efficacy, and quality-of-life measures in individuals with Parkinson disease. Physiother. Can. 63, 47–57 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  64. Miller, E. Verbal fluency as a function of a measure of verbal intelligence and in relation to different types of cerebral pathology. Br. J. Clin. Psychol. 23, 53–57 (1984).

    Article  PubMed  Google Scholar 

  65. Stamelou, M. et al. Power calculations and placebo effect for future clinical trials in progressive supranuclear palsy. Mov. Disord. 31, 742–747 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank Biogen (Cambridge, MA, USA), who sponsored this study and provided medical writing and editorial support for the development of this publication. We thank S. Douthwaite and M. Mandle (Excel Medical Affairs, Fairfield, CT, USA), who wrote the first draft of the manuscript based on input from the authors, and J. Parker (Excel Medical Affairs, Horsham, UK), who copyedited and styled the manuscript according to journal requirements. Biogen reviewed and provided feedback on the paper to the authors. All authors had full access to the study data, contributed to data interpretation and manuscript development, provided final approval for submission and take responsibility for data completeness and accuracy. The corresponding author had final responsibility for the decision to submit for publication. We thank the patients with PSP who participated in the PASSPORT trial, their families, the PASSPORT study group investigators and the clinical research centers where the study occurred. This research was carried out in part by the National Institutes for Health Research (NIHR) UCLH Clinical Research Facility in the United Kingdom. We also thank T. Olsson and M. Tighe for their contributions to the study design, and V. Kurnala (lead statistical programmer for the study) for his contribution to data analysis.

Author information

Authors and Affiliations

  1. Biogen, Cambridge, MA, USA

    Tien Dam, Lili Yang, Beth Tidemann-Miller, Joseph Kupferman, Kristine Harper, Kubra Kamisoglu, Michael J. Wald, Danielle L. Graham, Liz Gedney, John O’Gorman & Samantha Budd Haeberlein

  2. Memory and Aging Center, Department of Neurology, University of California, San Francisco, CA, USA

    Adam L. Boxer

  3. Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA

    Lawrence I. Golbe

  4. Department of Neurology, Technische Universität München, Munich, Germany

    Günter U. Höglinger

  5. German Center for Neurodegenerative Diseases, Munich, Germany

    Günter U. Höglinger

  6. Department of Neurology, Hanover Medical School, Hanover, Germany

    Günter U. Höglinger

  7. National Hospital for Neurology and Neurosurgery, London, UK

    Huw R. Morris

  8. University of California, Parkinson and Other Movement Disorders Center, San Diego, CA, USA

    Irene Litvan & Michael Grundman

  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

    Anthony E. Lang

  10. Sorbonne Université, Assistance Publique Hôpitaux de Paris, INSERM, CNRS, Institut du Cerveau – Paris Brain Institute – ICM, Hôpital Pitié-Salpêtrière, Paris, France

    Jean-Christophe Corvol

  11. Department of Neurology, National Hospital Organization Higashinagoya National Hospital, Nagoya, Japan

    Ikuko Aiba

  12. Global R&D Partners, LLC, San Diego, CA, USA

    Michael Grundman

Authors
  1. Tien Dam
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Adam L. Boxer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lawrence I. Golbe
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Günter U. Höglinger
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Huw R. Morris
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Irene Litvan
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Anthony E. Lang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jean-Christophe Corvol
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Ikuko Aiba
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Michael Grundman
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Lili Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Beth Tidemann-Miller
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Joseph Kupferman
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Kristine Harper
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Kubra Kamisoglu
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Michael J. Wald
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Danielle L. Graham
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Liz Gedney
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. John O’Gorman
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Samantha Budd Haeberlein
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

PASSPORT Study Group

Contributions

T.D. performed data analysis, interpretation and writing of the manuscript. A.L.B. carried out study design, data collection, data analysis, data interpretation, participant recruitment and writing of the report. L.I.G. oversaw development and implementation of the primary endpoint instrument, study design, participant recruitment, data collection, data interpretation, writing of the report and approval of the final version of the manuscript. G.U.H. performed study design, participant recruitment, data collection, data interpretation, writing of the report and approval of the final version of the manuscript. H.R.M. carried out study design, data collection, data interpretation, participant recruitment and critical review of the report. I.L. was responsible for study design, data collection, data interpretation, participant recruitment and critical review of the report. A.E.L. performed study design, data analysis, data interpretation, review of the manuscript and approval of the final version of the manuscript. J.-C.C. oversaw study design, data collection, data interpretation, participant recruitment and reviewing the manuscript. I.A. was responsible for study design, participant recruitment, data collection, data interpretation and reviewing of the manuscript. M.G. carried out study design, statistical analysis plan design, data collection, data interpretation and writing of the report. L.Y. was responsible for data analysis, data interpretation and writing of the manuscript. B.T.-M. performed data analysis, data interpretation and writing of the manuscript. J.K. carried out data analysis, data interpretation and writing of the report. K.H. oversaw data analysis, data interpretation and writing of the report. K.K. undertook data analysis, data interpretation and writing of the manuscript. M.J.W. performed data collection, data analysis, data interpretation and writing of the report. D.L.G. carried out study design, data analysis, data interpretation and writing of the manuscript. L.G. performed clinical operations and reviewing the manuscript. J.O. was responsible for data analysis, data interpretation and writing of the manuscript. S.B.H. undertook data analysis, interpretation and writing of the manuscript.

Corresponding author

Correspondence to Tien Dam.

Ethics declarations

Competing interests

A.L.B. reports consultancies for AGTC, Alector, Arkuda, Arvinas, Asceneuron, AZTherapies, Bioage, GSK, Humana, Lundbeck, Ono, Roche, Samumed, Sangamo, Stealth Therapeutics, Third Rock, Transposon, UCB and Wave, and research support from the Association for Frontotemporal Degeneration, Biogen, Bluefield Project to Cure Frontotemporal Dementia, Eli Lilly, Eisai, National Institutes of Health (grant nos. U19AG063911, U54NS092089 and R01AG031278) and Tau Research Consortium. L.I.G. reports consultancies for AbbVie, AlzProtect, Asceneuron, Biogen, CurePSP, Martin, Mitochon, Mitsubishi Tanabe, Pinteon, Retrotope, Roche, Stealth BioTherapeutics and UCB, and research support from AbbVie, American Parkinson’s Disease Association and Biogen. G.U.H. reports consultancies for AbbVie, AlzProtect, Asceneuron, Biogen, Biohaven, Lundbeck, Novartis, Roche, Sanofi and UCB; honoraria for scientific presentations from AbbVie, Bayer Vital, Bial, Biogen, Bristol-Myers Squibb, Roche, Teva, UCB and Zambon; research collaborations with Orion, Prothena and Roche; research support from GE Health, Neuropore, German Research Foundation (DFG; EXC 2145 SyNergy, nos. 390857198, HO2402/6-2 and HO2402/18-1), the German Federal Ministry of Education and Research (BMBF, nos. 01KU1403A and 01EK1605A), the NOMIS foundation (FTLD project), the EU/EFPIA/Innovative Medicines Initiative (2) Joint Undertaking (IMPRIND, grant no. 116060) and VolkswagenStiftung/Lower Saxony Ministry for Science/Petermax-Müller Foundation (Niedersächsisches Vorab). H.R.M. reports consultancies for AbbVie, Biogen, Biohaven, Denali and UCB; employment by North Thames National Institute for Health Research and University College London; lecture fees/honoraria from Biogen, C4X Discovery, Movement Disorders Society, UCB and Wellcome Trust; research grants from CBD Solutions, Cure Parkinson’s Trust, Drake Foundation, Medical Research Council, MND Association, Parkinson’s UK and PSP Association; and being a coapplicant on a patent application related to C9ORF72 (method for diagnosing a neurodegenerative disease (no. PCT/GB2012/052140)). I.L. reports scientific advisory board membership for Corticobasal Degeneration Solutions and Lundbeck; research support from AbbVie, Biogen, Biohaven, EIP-Pharma, Roche, Lewy Body Association, Michael J. Fox Foundation, National Institutes of Health (grant nos. 5P50AG005131-33, 2R01AG038791-06A, U01NS090259, U01NS100610, U01NS80818, R25NS098999, P20GM109025, U19AG063911-1 and 1R21NS114764-01A1) and Parkinson Foundation and Parkinson Study Group; and employment at University of California San Diego and Chief Editor of Frontiers in Neurology. A.E.L. reports advisory board membership for AbbVie, AFFiRis, Biogen, Corticobasal Degeneration Solutions, Janssen, Jazz Pharma, Lilly, Lundbeck, Merck, Paladin, PhotoPharmics, Roche, Sunovion, Sun Pharma and Theravance; honoraria from AbbVie, Sunovion and Sun Pharma; grants from Brain Canada, Canadian Institutes of Health Research, Corticobasal Degeneration Solutions, Edmond J. Safra Philanthropic Foundation, Michael J. Fox Foundation, Ontario Brain Institute, the Parkinson Foundation and Parkinson Society Canada. J.-C.C. reports advisory board membership for Pfizer; consultancies for Air Liquide, AlzProtect, Biogen, Bristol-Myers Squibb, Denali and Theranexus; speaker fees from Biogen and Ever Pharma; research grants from Actelion and Michael J. Fox Foundation; and travel grants from MDS. I.A. reports consultancies for AbbVie and Biogen. M.G. reports consultancies for Biogen and Bristol-Myers Squibb. T.D., L.Y., B.T.-M., K.K., M.J.W., D.L.G., L.G., J.O. and S.B.H. are employees of, and hold stock in, Biogen. J.K. is a former employee of, and holds stock in, Biogen. K.H. reports being an independent physician pharmacovigilance professional at Biogen for the PASSPORT study.

Additional information

Peer review information Nature Medicine thanks Chengjie Xiong and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. Jerome Staal was the primary editor on this article and managed its editorial process and peer review in collaboration with the rest of the editorial team.

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Extended data

Extended Data Fig. 1 Participant Disposition in the PASSPORT study.

Percentages are based on the number of participants who received study drug. *Three participants randomly assigned to placebo received one dose of gosuranemab. †One participant assigned to placebo was not dosed due to abnormal vital signs, and three participants assigned to gosuranemab were not dosed because they failed to meet randomization criteria.

Supplementary information

Supplementary Information

Supplementary Tables 1 and 2 and Fig. 1.

Reporting Summary

Source data

Source Data Fig. 1

Statistical source data.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Dam, T., Boxer, A.L., Golbe, L.I. et al. Safety and efficacy of anti-tau monoclonal antibody gosuranemab in progressive supranuclear palsy: a phase 2, randomized, placebo-controlled trial. Nat Med 27, 1451–1457 (2021). https://doi.org/10.1038/s41591-021-01455-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41591-021-01455-x

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing