[HTML][HTML] 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 …

EA King, JW Davis, JF Degner - PLoS genetics, 2019 - journals.plos.org
PLoS genetics, 2019journals.plos.org
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 …
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.
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