Human Genetics and Drug Development

This article explores how human genetics can inform drug development by distinguishing between target-mediated and off target effects of therapeutic interventions. The author discusses the use of genetic variants, such as those in ACLY, HMGCR, and PCSK9, to predict the efficacy and safety of drugs like bempedoic acid, an ATP citrate lyase (ACL) inhibitor. Mendelian randomization studies reveal that ACL inhibition shares cardiovascular benefits with statins but may have unique pleiotropic effects, such as a reduced risk of diabetes. However, off-target adverse effects (e.g., gout) observed in clinical trials cannot be predicted genetically. The integration of genetic data with clinical trials, including ongoing studies like CLEAR Outcomes, promises to refine drug development strategies and improve therapeutic precision.

This article explores how human genetics can inform drug development by distinguishing between target-mediated and off target effects of therapeutic interventions. The author discusses the use of genetic variants, such as those in ACLY, HMGCR, and PCSK9, to predict the efficacy and safety of drugs like bempedoic acid, an ATP citrate lyase (ACL) inhibitor. Mendelian randomization studies reveal that ACL inhibition shares cardiovascular benefits with statins but may have unique pleiotropic effects, such as a reduced risk of diabetes. However, off-target adverse effects (e.g., gout) observed in clinical trials cannot be predicted genetically. The integration of genetic data with clinical trials, including ongoing studies like CLEAR Outcomes, promises to refine drug development strategies and improve therapeutic precision.