Are drug targets with genetic support twice as likely to be approved? Revised estimates of the impact of genetic support for drug mechanisms on the probability of drug approval

Despite strong vetting for disease activity, only 10% of candidate new molecular entities in early stage clinical trials are eventually approved. Analyzing historical pipeline data, Nelson et al. 2015 (Nat. Genet.) concluded pipeline drug targets with human genetic evidence of disease association ar...

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Bibliographic Details
Published in:PLoS genetics 2019-12, Vol.15 (12), p.e1008489-e1008489
Main Authors: King, Emily A, Davis, J Wade, Degner, Jacob F
Format: Article
Language:English
Subjects:
Biology and Life Sciences
Cardiovascular disease
Clinical trials
Computer and Information Sciences
Databases, Genetic
Datasets
Drug Approval - statistics & numerical data
Drug development
Drugs
Estimates
Genes
Genetic Predisposition to Disease
Genome-Wide Association Study
Genomics
Genomics - methods
Humans
Mathematical models
Medicine and Health Sciences
Methods
Models, Statistical
Mutation
Pharmaceutical industry
Pharmacogenomic Variants
Phenotype
Precision Medicine
Quantitative Trait Loci
Research and Analysis Methods
Statistical analysis
Success
Therapeutic targets
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Summary:Despite strong vetting for disease activity, only 10% of candidate new molecular entities in early stage clinical trials are eventually approved. Analyzing historical pipeline data, Nelson et al. 2015 (Nat. Genet.) concluded pipeline drug targets with human genetic evidence of disease association are twice as likely to lead to approved drugs. Taking advantage of recent clinical development advances and rapid growth in GWAS datasets, we extend the original work using updated data, test whether genetic evidence predicts future successes and introduce statistical models adjusting for target and indication-level properties. Our work confirms drugs with genetically supported targets were more likely to be successful in Phases II and III. When causal genes are clear (Mendelian traits and GWAS associations linked to coding variants), we find the use of human genetic evidence increases approval by greater than two-fold, and, for Mendelian associations, the positive association holds prospectively. Our findings suggest investments into genomics and genetics are likely to be beneficial to companies deploying this strategy.
ISSN:1553-7404
1553-7390
1553-7404
DOI:10.1371/journal.pgen.1008489