Trends in early drug safety.

Successful introduction of a new drug to the market is not only an extremely costly and complicated process, but also fraught with a substantial risk of failure. The number of new drugs launched each year from 1990 to 2000 has stayed relatively constant, while the cost of pharmaceutical research and development has risen by almost 2.5-fold over the same period. What is not revealed by these figures is that the chance of success for a drug candidate passing through the various hurdles in pharmaceutical development is at best 1 in 10 and has barely changed despite advancing technology in other areas of research and development. While we expect high failure rates in drug discovery, it is of substantial concern that most candidates in development on which large investments have already been made are probably not going to make any return. A major stumbling block is the absorption, distribution, metabolism, excretion and toxicology profile of drug candidates. These issues were discussed at the Society for Medicines Research symposium held September 18, 2003, in London, United Kingdom. Recent SMR symposia have focused on the ADME and pharmacokinetic aspects of drug discovery and development. Indeed, it is now uncommon for drug discovery projects not to address these issues early in their lifetimes. Although it is less common to address drug safety early in a project, it is being utilized more frequently to help select the best clinical candidates for further development. This meeting report summarizes some of the key aspects of early drug safety issues facing the drug discoverer today. Classical approaches to toxicology, p450-mediated safety, cardiovascular safety, "omics" approaches and their impact upon clinical safety will be discussed.