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Moving towards early clinical trials for amyloid-targeted therapy in Alzheimer's disease

Nature Reviews Drug Discovery volume 12, page 324 (2013)Cite this article

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A recent article in Nature Reviews Drug Discovery (Nature Rev. Drug Discov. 11, 657–660; 2012)1 highlighted the outcome of the two largest Alzheimer's disease drug development programmes to date. Results from the Phase III clinical trials of two monoclonal antibodies — bapineuzumab and solanezumab — that target amyloid-β indicated little clinical benefit of immunological attack on amyloid-β at the dementia stage of sporadic disease2 (see the 12 December 2012 press release on the Lilly website).

Neither antibody demonstrated a favourable impact on the primary cognitive assessment scores and inventories of daily function in patients with mild to moderate Alzheimer's disease-related dementia. However, planned post-hoc pooled analyses of data from individuals with mild Alzheimer's disease-related dementia treated with solanezumab did show cognitive benefit, so the development of this agent for the treatment of Alzheimer's-related dementia will continue with a confirmatory clinical trial planned for launch later this year (See the 12 December 2012 press release on the Lilly website).

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Figure 1: Hypothetical results of an early Alzheimer's disease clinical trial.

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Acknowledgements

P.S.A.'s work is supported by grants from the US National Institute on Aging of the US National Institutes of Health. B.V.'s work is supported by Gerontopole, CHU, INSERM UMR 1027, University of Toulouse. H.H.'s work is supported by grants from the Katharina-Hardt-Foundation, Bad Homburg, Germany.

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Authors and Affiliations

  1. Paul S. Aisen is at the Department of Neurosciences, University of California, San Diego, 9500 Gilman Drive M/C 0949, San Diego, California 92093, USA.,

    Paul S. Aisen

  2. Bruno Vellas is at the Department of Internal Medicine and Geriatrics, Toulouse University Hospital, 170 Avenue de Casselardit, TSA 40031, 31059 Toulouse Cédex 9, France.,

    Bruno Vellas

  3. Harald Hampel is at the Department of Psychiatry, University of Frankfurt, Heinrich-Hoffman-Str. 10, 60528 Frankfurt, Germany.,

    Harald Hampel

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Correspondence to Paul S. Aisen.

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Competing interests

Paul S. Aisen serves on a scientific advisory board for NeuroPhage; he has served as a consultant to Elan Corporation, Wyeth, Eisai, Schering-Plough, Bristol-Myers Squibb, Eli Lilly and Company, NeuroPhage, Merck & Co., Roche, Amgen, Genentech, Abbott, Pfizer, Novartis, Bayer, Astellas Pharma, Dainippon, Biomarin, Solvay, Otsuka, Daiichi, AstraZeneca, Janssen, Medivation, Ichor, Toyama, Lundbeck, Biogen Idec, iPerian, Probiodrug, Somaxon, Biotie, Anavex and Kyowa Hakko Kirin Pharma; and he receives research support from Eli Lilly and Company and Baxter International.

Bruno Vellas has served as a consultant to Elan Corporation, Schering-Plough, Bristol-Myers Squibb, Eli Lilly and Company, Merck & Co., Roche, Genentech, Pfizer, Novartis, AstraZeneca, Janssen, Medivation, Nestle and Nutritia; he receives research support from Pierre Fabre, and has received several grants from the European Commission and the Public Health Research Consortium programme.

Harald Hampel has, during the past two years (2011 to 2013), received lecture honoraria and/or research grants and/or travel funding and/or participated in scientific advisory boards and/or served as a consultant to diagnostic, biotechnology and pharmaceutical companies involved in the manufacture and marketing of biomarkers and/or diagnostics and/or drugs or medicinal products for cognitive impairment and/or Alzheimer's disease. These companies include Boehringer-Ingelheim, Bristol-Myers Squibb, Elan Corporation, Wyeth, Novartis, Eisai, Pfizer, Schwabe, Sanofi-Aventis, Roche Pharmaceuticals and Diagnostics, GE Healthcare, Astra-Zeneca, Avid, Eli Lilly and Company, Janssen-Cilag, Merz Pharmaceuticals, GlaxoSmithKline-Biologicals, Jung-Diagnostics and Thermo Fisher Scientific Clinical Diagnostics. He is co-inventor in pending patent submissions relating to biological markers and/or diagnostics but has not received any royalties.

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Aisen, P., Vellas, B. & Hampel, H. Moving towards early clinical trials for amyloid-targeted therapy in Alzheimer's disease. Nat Rev Drug Discov 12, 324 (2013). https://doi.org/10.1038/nrd3842-c1

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