Signals in man
The discovery and sequencing of the vast majority of potential targets has left the industry with a glut of information and a value chain where the benefits of industrialization decrease as development proceeds downstream, leaving companies searching for effective ways to transition from target identification to isolating viable drug candidates.
Further downstream, the disconnect between many animal models and proof of concept in humans has many companies searching for ways to decrease the attrition rate in late preclinical development, and increase the continuity between discovery and development.
In some cases, the answers may best come by testing compounds in humans, using very small doses to answer critical path questions about pharmacokinetics, pharmacodynamics, and/or receptor binding characteristics without endangering the test subjects.
In fact, some pharma companies have for years done pre-Phase I exploratory studies in humans. While the practice has been far from commonplace, it might rise in the future, as new technologies and analytical methods could expand the scope and utility of so-called microdose trials.
Indeed, the push to get into humans quicker is felt by many companies.
"Everybody is looking for ways to improve pharmaceutical productivity," said Dennis Giesing, senior vice president of lead optimization at Aventis S.A. (AVE, Strasbourg, France). "One is to try to move into man as quickly as possible, and microdosing studies are just one element of this approach."
"A real question is how valid and how predictive animal models are," said Mark Fishman, global head of research and president of the Novartis Institute of Biomedical Research Inc. (Cambridge, Mass.).
In oncology, Fishman noted, the lack of an animal