抄録
High failure rates, rising costs of drug development, and patent expiration has forced the pharmaceutical industry to transform its business model. One area that has made significant progress in this transformation is how toxicology is applied within the pharmaceutical industry. Within Pfizer, survival rates at the start of the 21st century were as low as 50% with the majority of failures due to safety. Moving toxicology into the discovery space, referred to as “Discovery Toxicology”, has enabled Pfizer to currently reach preclinical survival rates approaching 90%. This required new thinking, new assays and a new approach to how targets and compounds are selected. Attrition due to genetic toxicology or QT prolongation has been eliminated entirely. Case studies will be provided that outline how attrition has been moved from regulatory toxicology studies to early stages of the discovery process. Examples will include how to leverage toxicological data to prioritize new targets in the early discovery phases, development of novel in vitro assays for structure activity relationship and how novel in vivo paradigms are used to nominate lead molecules. In addition, a case study related to de-risking a kinase program will demonstrate how to differentiate cardiac toxicities deemed a class effect. Although attrition still remains a concern for the pharmaceutical industry, attrition related to safety has been significantly reduced within Pfizer, thus saving the organization millions of dollars and the ability to focus resources on successful programs.
