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The support of human genetic evidence for approved drug indications

Matthew R Nelson1, Hannah Tipney2, Jeffery L Painter1

  • 1Quantitative Sciences, GlaxoSmithKline, Research Triangle Park, North Carolina, USA.

Nature Genetics
|June 30, 2015
PubMed

Insights

Leveraging human genetic data to select drug targets and indications could significantly improve drug development success rates. Genetically supported targets show a higher success probability, potentially doubling the current success rate.

Area of Science:

  • Pharmacology
  • Genetics
  • Drug Development

Background:

  • A significant portion of drugs fail in clinical development due to ineffectiveness.
  • Human genetic insights are increasingly influencing drug target and indication selection.
  • Guidance is lacking on the weight to be given to genetic evidence in these critical decisions.

Purpose of the Study:

  • To investigate the predictive power of current genetic evidence for drug mechanisms.
  • To quantify the association between genetic support and drug development success.

Main Methods:

  • Analysis of genetic evidence archives to assess support for drug mechanisms.
  • Examination of drug mechanisms across different stages of the drug development pipeline.
  • Comparison of genetic support proportions between preclinical and approved drugs.

Main Results:

  • The proportion of drug mechanisms with direct genetic support increases from 2.0% in preclinical stages to 8.2% for approved drugs.
  • Genetic support for drug mechanisms varies considerably across different disease areas.
  • Selecting genetically supported targets is estimated to double the success rate in clinical development.

Conclusions:

  • Human genetic data offers a powerful tool for optimizing drug target and indication selection.
  • Integrating genetic evidence can substantially enhance the efficiency and success of new drug development.
  • Further utilization of genetic insights is recommended to improve the drug development pipeline.

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