The support of human genetic evidence for approved drug indications.


Nelson, MR; Tipney, H; Painter, JL; Shen, J; Nicoletti, P; Shen, Y; Floratos, A; Sham, PC; Li, MJ; Wang, J; Cardon, LR; Whittaker, JC; Sanseau, P; (2015) The support of human genetic evidence for approved drug indications. Nature genetics, 47 (8). pp. 856-60. ISSN 1061-4036 DOI: https://doi.org/10.1038/ng.3314

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Abstract

Over a quarter of drugs that enter clinical development fail because they are ineffective. Growing insight into genes that influence human disease may affect how drug targets and indications are selected. However, there is little guidance about how much weight should be given to genetic evidence in making these key decisions. To answer this question, we investigated how well the current archive of genetic evidence predicts drug mechanisms. We found that, among well-studied indications, the proportion of drug mechanisms with direct genetic support increases significantly across the drug development pipeline, from 2.0% at the preclinical stage to 8.2% among mechanisms for approved drugs, and varies dramatically among disease areas. We estimate that selecting genetically supported targets could double the success rate in clinical development. Therefore, using the growing wealth of human genetic data to select the best targets and indications should have a measurable impact on the successful development of new drugs.

Item Type: Article
Faculty and Department: Faculty of Epidemiology and Population Health > Dept of Non-Communicable Disease Epidemiology
PubMed ID: 26121088
Web of Science ID: 358674100006
URI: http://researchonline.lshtm.ac.uk/id/eprint/2293134

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