Drug Development for Alzheimer's Disease: Where Are We Now and Where Are We Headed?

Objective: The aim of this article was to provide a survey of the clinical development of pharmacotherapy for Alzheimer's disease (AD). Methods: A search of PubMed to identify pertinent English-language literature was conducted using the terms Alzheimer's disease AND clinical trials (2003-2008), dementia AND prevention AND clinical trials (20032008), and the chemical names of all compounds mentioned in articles on new drugs for AD published since 2005. www.Clinicaltrials.gov was searched for relevant trials. Abstracts of the 2008 International Conference on Alzheimer's Disease (ICAD) were reviewed for relevance, as were pharmaceutical company and AD advocacy Web sites. Articles selected for review were primary reports of data from preclinical studies and clinical trials. Results: A large number of drugs with differing targets and mechanisms of action are under development for the treatment of AD. Phase III trials of Ginkgo biloba, NSAIDs, phenserine, statins, tarenflurbil, tramiprosate, and xaliproden have been completed, none of them demonstrating adequate efficacy. Encouraging results from completed Phase II trials of dimebon, huperzine A, intravenous immunoglobulin, and methylthioninium chloride were reported at ICAD 2008. Nineteen compounds are currently in Phase II trials, and 3 compounds (AN1792, lecozotan SR, and SGS742) failed at this stage of development. Conclusions: Despite disappointing results from recently completed Phase III trials of several novel compounds, the extent and breadth of activity at all phases of clinical development suggest that new pharmacotherapeutic options for the treatment of AD will become available within the next decade. (Am J Geriatr Pharmacother. 2009;7:167185) (C) 2009 Excerpta Medica Inc.