Use of toxicogenomics in drug safety evaluation: Current status and an industry perspective

• Published in: Regulatory toxicology and pharmacology 2018-07, Vol.96, p.18-29
• Main Authors: Vahle, John L., Anderson, Ulf, Blomme, Eric A.G., Hoflack, Jean-Christophe, Stiehl, Daniel P.
• Format: Article
• Language: English
• Subjects: Animals; Drug development; Drug discovery; Drug Evaluation, Preclinical - adverse effects; Drug Industry; Drug safety; Humans; Predictive toxicology; Toxicogenetics; Toxicogenomics
• ISSN: 0273-2300; 1096-0295
• DOI: 10.1016/j.yrtph.2018.04.011

Toxicogenomics held great promise as an approach to enable early detection of toxicities induced by xenobiotics; however, there remain questions regarding the impact of the discipline on pharmaceutical nonclinical safety assessment. To understand the current state of toxicogenomics in the sector, an industry group surveyed companies to determine the frequency of toxicogenomics use in in vivo studies at various stages of drug discovery and development and to assess how toxicogenomics use has evolved over time. Survey data were compiled during 2016 from thirteen pharmaceutical companies. Toxicogenomic analyses were infrequently conducted in the development phase and when performed were done to address specific mechanistic questions. Prior to development, toxicogenomics use was more frequent; however, there were significant differences in approaches among companies. Across all phases, gaining mechanistic insight was the most frequent reason cited for pursing toxicogenomics with few companies using toxicogenomics to predict toxicities. These data were consistent with the commentary submitted in response to survey questions asking companies to describe the evolution of their toxicogenomics strategy. Overall, these survey data indicate that toxicogenomics is not widely used as a predictive tool in the pharmaceutical industry but is used regularly by some companies and serves a broader role in mechanistic investigations and as a complement to other technologies. •Thirteen companies contributed survey data to understand how toxicogenomic approaches are used in drug discovery and development.•Gathering mechanistic insight was the most frequently cited reason to conduct a toxicogenomic analysis.•Toxicogenomic analysis was conducted more frequently early in drug discovery rather than during clinical development.•Toxicogenomics is not widely used to predict toxic responses, but can be a powerful tool for mechanistic research.