TY - JOUR
KW - Chromosome Mapping
KW - Databases, Genetic
KW - Drug Approval
KW - Genetic Association Studies
KW - Genetic Predisposition to Disease
KW - Genetics, Medical
KW - Genome-Wide Association Study
KW - Humans
KW - Linkage Disequilibrium
KW - Medical Subject Headings
KW - Molecular Targeted Therapy
KW - Polymorphism, Single Nucleotide
AU - Matthew R. Nelson
AU - Hannah Tipney
AU - Jeffery L. Painter
AU - Judong Shen
AU - Paola Nicoletti
AU - Yufeng Shen
AU - Aris Floratos
AU - Pak Chung Sham
AU - Mulin Jun Li
AU - Junwen Wang
AU - Lon R. Cardon
AU - John C. Whittaker
AU - Philippe Sanseau
AB - 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.
BT - Nature Genetics
DA - 2015-08
DO - 10.1038/ng.3314
IS - 8
LA - eng
N2 - 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.
PY - 2015
SP - 856
EP - 860
T2 - Nature Genetics
TI - The support of human genetic evidence for approved drug indications
VL - 47
SN - 1546-1718
ER -