which accounts for about 15,000 new diagnoses per year in the United States. In partnership with the University of Kansas and the Leukemia & Lymphoma Society, NCATS screened the NPC collection for effects against CLL patient cells as well as against cells from normal donors. Some drugs killed the CLL cells from all patients, while some killed the cells from only some of the patients. Subsets of these drugs were less effective or ineffective in killing normal donor cells. One particular drug called Auranofin was originally approved for the treatment of rheumatoid arthritis in 1984. Reverse pharmacology revealed the mechanism of action of the drug, and three clinical trial sites are now active.
The principal lesson Austin drew from this experience is that effective translation requires collaboration. The partnership benefited by the marriage of funding sources, expertise, project management, and the early incorporation of technology transfer agreements which allowed for rapid movement in establishing the trials. In fact, less than a year passed between signing the partnership agreement and the dosing of the first patients. “This is a great example of how, [through] a team effort, we were able to move forward.”
One complication in the repurposing of drugs is that about 90 percent of the drugs in the pharmaceutical collection are generic. For these drugs, paying for a registration trial to expand the indication can be a barrier. In addition, regulatory issues can impede the repurposing of on-patent or abandoned drugs. For example, one might wish to know if the new indication is related to the original mechanism of action or if it is related to an unexpected or unrelated mechanism. Or if the mode of delivery is the same. To answer such questions, it is typically the case that data are needed from the firm that originally created the drug.
Public policy changes may be necessary to encourage drug repurposing. For example, establishing exclusivity could allow the licensing of a discovery to a for-profit organization to take a drug through registration. Also, it is never too early to start thinking about reimbursement strategies, Austin said, because the goal is to get the drug to patients.
A Value Maximization Path, or ValueMaP, is under development to provide guidance in pursing drug repurposing. This guidance draws on examples of what has worked in previous projects, such as rational repurposing based on knowledge of disease pathogenesis and drug pharmacology. In addition, in selected cases computational approaches have been able to identify promising pathways or patterns (Sirota et al., 2011).
Partnerships need comprehensive and complementary expertise at every step of the process, Austin said. When the process breaks down, it often does so in the experimental medicine space, such as in the early clinical trials. Other problems have arisen when repurposing is based solely on animal models, when computational approaches are used without experi-