Why has therapy development for dementia failed in the last two decades?

TitleWhy has therapy development for dementia failed in the last two decades?
Publication TypeJournal Article
Year of Publication2016
AuthorsGauthier S, Albert M, Fox N, Goedert M, Kivipelto M, Mestre-Ferrandiz J, Middleton LT
JournalAlzheimers Dement
Date Published2016 Jan
KeywordsAlzheimer Disease, Biomarkers, Cholinesterase Inhibitors, Clinical Trials as Topic, Dementia, Drug Discovery, Humans, Memantine, Treatment Failure

The success rate of the pharmaceutical research and development (R&D) for dementia drugs has been abysmally low, in the last two decades. Also low has been the number of pipeline drugs in development, compared to other therapy areas. However, the rationale of early terminations has not been reported in the majority of trials. These are key findings of the recently published pharmaceutical pipeline analysis by the UK-based Office of Health Economics (OHE). Our understanding of main challenges include (1) the significant gaps of knowledge in the nosology and complexity of the underpinning biological mechanisms of the commonest, not familial, forms of late onset dementias; (2) low signal-to-noise ratio, notwithstanding the lack of validated biomarkers as entry and/or end-point criteria; (3) recruitment and retention, particularly in the asymptomatic and early disease stages. A number of current and future strategies aimed at ameliorating drug development are outlined and discussed.

Alternate JournalAlzheimers Dement
PubMed ID26710325
Grant ListMC_U105184291 / / Medical Research Council / United Kingdom