Journal article

A trial of gantenerumab or solanezumab in dominantly inherited Alzheimer's disease

Stephen Salloway, Martin Farlow, Eric McDade, David B Clifford, Guoqiao Wang, Jorge J Llibre-Guerra, Janice M Hitchcock, Susan L Mills, Anna M Santacruz, Andrew J Aschenbrenner, Jason Hassenstab, Tammie LS Benzinger, Brian A Gordon, Anne M Fagan, Kelley A Coalier, Carlos Cruchaga, Alison A Goate, Richard J Perrin, Chengjie Xiong, Yan Li Show all

NATURE MEDICINE | NATURE RESEARCH | Published : 2021

Abstract

Dominantly inherited Alzheimer's disease (DIAD) causes predictable biological changes decades before the onset of clinical symptoms, enabling testing of interventions in the asymptomatic and symptomatic stages to delay or slow disease progression. We conducted a randomized, placebo-controlled, multi-arm trial of gantenerumab or solanezumab in participants with DIAD across asymptomatic and symptomatic disease stages. Mutation carriers were assigned 3:1 to either drug or placebo and received treatment for 4-7 years. The primary outcome was a cognitive end point; secondary outcomes included clinical, cognitive, imaging and fluid biomarker measures. Fifty-two participants carrying a mutation wer..

View full abstract

Grants

Awarded by NIA of the NIH


Awarded by NIA of the NIH (DIAN)


Funding Acknowledgements

We gratefully acknowledge the outstanding commitment of the participants, family members and caregivers whose participation was critical to the success of the DIAN-TU trial. We thank the DIAN-TU Funding and Study Team (https://dian.wustl.edu/our-research/clinical-trial/funding/) for their exceptional dedication and accomplishments, which ensured the success of the trial. We thank the DIAN-EXR and DIAN-OBS study teams for their support on recruitment and commitment to family members. We acknowledge the robust intellectual collaboration between the DIAN-TU investigators, participants and family members, F. Hoffmann-La Roche, Ltd/Genentech and Eli Lilly and Company, the DIAN-TU Pharma Consortium (https://dian.wustl.edu/our-research/the-pharma-consortium/), the NIH, and regulatory representatives who were critical in making this study possible. We thank the Alzheimer's Association, GHR Foundation, an anonymous organization, other industry partners (Avid Radiopharmaceuticals, a wholly-owned subsidiary of Eli Lilly and Company, Signant Health and Cogstate) and regulatory representatives for their support. We also thank L. Ryan from the National Institute on Aging (NIA) for her key contributions in leadership and scientific guidance on this project. The research reported in this publication was supported by the NIA of the NIH under award nos. U01AG042791, U01AG042791-S1 (FNIH and Accelerating Medicines Partnership), R01AG046179 and R01AG053267-S1. This research was also supported by the Alzheimer's Association, Eli Lilly and Company, F. Hoffman-LaRoche Ltd, Avid Radiopharmaceuticals GHR Foundation and an anonymous organization. Cogstate and Signant Health offered in-kind support. The DIAN-OBS was supported by the NIA of the NIH (DIAN, U19AG032438), the German Center for Neurodegenerative Diseases, Raul Carrea Institute for Neurological Research, partial support by the Research and Development Grants for Dementia from the Japan Agency for Medical Research and Development (AMED) and the Korea Health Technology R&D Project through the Korea Health Industry Development Institute.