Format

Send to

Choose Destination
Nat Genet. 2015 Aug;47(8):856-60. doi: 10.1038/ng.3314. Epub 2015 Jun 29.

The support of human genetic evidence for approved drug indications.

Author information

1
Quantitative Sciences, GlaxoSmithKline, Research Triangle Park, North Carolina, USA.
2
Quantitative Sciences, GlaxoSmithKline, Stevenage, UK.
3
Department of Systems Biology, Columbia University, New York, New York, USA.
4
1] Department of Systems Biology, Columbia University, New York, New York, USA. [2] Department of Biomedical Informatics, Columbia University, New York, New York, USA.
5
1] State Key Laboratory of Brain and Cognitive Sciences, University of Hong Kong, Hong Kong, SAR, China. [2] Centre for Genomics Sciences, Li Ka Shing (LKS) Faculty of Medicine, University of Hong Kong, Hong Kong SAR, China.
6
1] Centre for Genomics Sciences, Li Ka Shing (LKS) Faculty of Medicine, University of Hong Kong, Hong Kong SAR, China. [2] Department of Biochemistry, LKS Faculty of Medicine, University of Hong Kong, Hong Kong SAR, China.
7
Alternative Discovery and Development, GlaxoSmithKline, Upper Merion, Pennsylvania, USA.

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.

PMID:
26121088
DOI:
10.1038/ng.3314
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center