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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

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

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

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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.

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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

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  1. Tien Dam
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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.

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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.

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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.

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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.

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Source data

Source Data Fig. 1

Statistical source data.

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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

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

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