A Look at Pharmaceutical Industry’s Focus on Addressing Candidate Attrition
Due to Toxicology and ADME
Yue-Zhong Shu, Ph.D., MBA
Dr. Shu received his B.S. degree from China Pharmaceutical University (Nanjing) and a Ph.D. degree in Pharmaceutical Science from Toyama Medical and Pharmaceutical University (Japan) on the chemistry and biotransformation of bioactive natural products. He started his pharmaceutical industrial career in 1991 at Pfizer Central Research Division in the area of drug metabolism. Then he joined Bristol-Myers Squibb Pharmaceutical Research Institute, and became the Group Leader of Natural Products Chemistry responsible for natural products drug discovery. Dr. Shu is currently Associate Director of Pharmaceutical Candidate Optimization, an organization that focuses on the identification of superior drug candidates through the optimization of the physicochemical, ADME and safety attributes of molecules in order to increase success rates from drug candidate nomination to launch. His scientific and leadership experience include the discovery of synthetic and natural product drug candidates, drug metabolism and biotransformation, and strategies for drug candidate optimization. Dr. Shu has 45 publications in international scientific journals and holds 6 patents. He also earned an MBA degree to augment his skills in strategic, organizational and business issues.
The landscape of drug discovery and development at a global level has changed significantly over the last decade. The discovery of new medicines has become increasingly difficult, and associated cost become very high while the output of newly launched drugs has fallen. This is attributed to a number of important reasons: 1). There have been relatively few new and validated targets for new medicines. All drugs today hit only approximately 120 biological targets. The hurdle for target validation and “quality assurance” is increasingly high. 2). Problems of drug candidates in mechanism-related (or target-related) toxicity and off-target toxicity, physico-chemical property, and in absorption, distribution, metabolism, and excretion (ADME) have caused high degree of attrition in drug development. 3). There have been relatively few new predictive models and biomarkers to predict efficacy, toxicity, and fate of medicines in humans. 4). There is much variation between individuals to medicine. 5). There has been limitation in chemical universe of potential drug candidates despite the high hope for combinatory library to deliver diverse chemotypes.
The pharmaceutical R & D overarching goal in recent years has been to reduce the attrition rate of drug candidate during development by enhancing the quality of discovery compounds that lack major liabilities, especially toxicity and ADME problems. This presentation will discuss recent industry trend, as reflected in R & D strategies of a number of major pharmaceutical companies, to overcome hurdles in developability and tackle key productivity and attrition issues in the area of toxicology, drug metabolism and pharmacokinetics.