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

PLoS Genet. 2019 Dec 12;15(12):e1008489. doi: 10.1371/journal.pgen.1008489. eCollection 2019 Dec.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Databases, Genetic*
  • Drug Approval / statistics & numerical data*
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Genomics / methods
  • Humans
  • Models, Statistical
  • Pharmacogenomic Variants
  • Phenotype
  • Precision Medicine
  • Quantitative Trait Loci

Grant support

All authors are employees of AbbVie. The design, study conduct, and financial support for this research were provided by AbbVie. AbbVie participated in the interpretation of data, review, and approval of the publication.