Leading policy-makers and scholars explain how market forces, deregulation, and consumer choice can work to improve health care for all Americans.


Circumventing Resistance to Kinase-Inhibitor Therapy
Brian Druker, M.D., New England Journal of Medicine, 6-15-06

In a recent issue of the New England Journal Of Medicine, Brian Drucker, inventor of the powerful cancer drug Gleevec, offers a fascinating overview of recent efforts to, as it were, reverse engineer Gleevec in order to design new drugs to more effectively combat cancers that have become Gleevec-resistant. He also offers his thoughts as to why pharmaceutical companies have remained focused this small group of patients who have failed on the standard therapy.

These drugs were developed rapidly. A driving factor was the high quality of the basic science associated with clinical trials in CML. Mechanisms of relapse were rapidly identified, and the solution to the crystal structure of ABL in complex with [Gleevec] prompted rapid modification of the structure of the drug. Only a continued investment in a basic understanding of disease mechanisms will make possible similar advances.

It would be logical to ask why two large pharmaceutical companies would have an interest in a disease that affects fewer than 5000 patients per year in the United States and one in which drug resistance is relatively uncommon. One reason is that imatinib had gross sales of $2.1 billion in 2004. Although this volume of sales is not entirely attributable to its use in CML, it does mean that CML therapy is an attractive market. An encouraging thought is that some large pharmaceutical companies recognize the power of genomic medicine. They have an interest in testing a drug in a small, molecularly defined population, such as patients with imatinib-resistant CML. By limiting testing to a population with a high probability of having a response to therapy, the company reduces the risk of drug failure, and the number of patients who are required to demonstrate clinical activity of the drug can be relatively small. These two factors minimize the costs of drug development, could lead to rapid approval by the Food and Drug Administration, and might result in decreased drug costs.

Project FDA.
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