Until now, the UGT1A1 test has only been available to patients enrolled in studies at the University of Chicago. Third Wave had received FDA approval for its UGT1A1 test kit in August, but the test had not yet been made available to patients.
Through this licensing agreement, Mayo Clinic's reference laboratory, Mayo Medical Laboratories (MML), will make the test available to patients nationwide, starting this month.
The UGT1A1 test was developed and patented by Mark J. Ratain, M.D., the Leon O. Jacobson Professor of Medicine and Chairman of the Committee on Clinical Pharmacology and Pharmacogenomics at the University of Chicago, and colleagues. It gives doctors advance knowledge of an individual's risk for toxicity from irinotecan by revealing whether patients have one of two common versions of a gene that encodes for a protein involved in the metabolism of irinotecan.
"Although most patients tolerate the drug quite well, some patients are genetically predisposed to severe side effects from irinotecan treatment," said Ratain. "The UGT1A1 test enables us to know in advance which patients are at risk. Those patients could be given reduced doses of irinotecan or other chemotherapy drugs."
This kind of customized dosing based on a person's genetic makeup is known as pharmacogenomics and is at the forefront of 21st century medicine. The UGT1A1 test is part of a growing list of pharmacogenomic tests designed to help physicians personalize treatment options.
"Precise dosing is extremely important for cancer chemotherapy because many of these drugs are most effective at the highest possible dose yet they are also quite toxic," said Ratain. "But finding the right dose is difficult because patients vary radically and unpredictably in how they respond to these drugs. Our goal is to determine how an individual's genetic makeup controls the ways he or she responds to these drugs -- how the medications are absorbed, distributed in the body, broken down and eliminated -- and to use that knowledge to determine the best possible dose for each patient."
"Our early studies with irinotecan demonstrated that the highly variable toxicity was related to variability in the drug's metabolism," he said. "We subsequently found that patients with two copies of one version of the UGT1A1 gene had few side effects at the standard dosage. Patients with only one copy of this version had more difficulty, and patients with two copies of the alternative version were at high risk for severe side effects.
"So relying on one standard dose meant that some of those patients received sub-therapeutic doses of irinotecan and others received more than they could manage. We envision that dosing based on the UGT1A1 test will have the dual advantage of reducing side effects and increasing benefit of this important drug."
Because of this study, the FDA, on June 7, 2005, required amendment of the package insert for Camptosar® to include a warning that patients with a particular UGT1A1 genotype should receive a lower starting dose.
"With the growing interest in individualizing drug therapy, FDA's approval of this assay provides physicians and patients with important information on the proper dosage of drugs metabolized and cleared from the body by the UGT1A1 pathway," said Lawrence Lesko, Ph.D., Director of the FDA's Office of Clinical Pharmacology and Biopharmaceutics in the Center for Drug Evaluation and Research in a press release issued when the FDA approved UGT1A1 testing in August.
"Information on the UGT1A1 genotype can be an integral part of drug labels," he added, "and will guide health professionals on how to dose medications such as irinotecan."
Colorectal cancer is the fourth most commonly diagnosed cancer in the U.S., with more than 145,000 new cases per year in the U.S. It accounts for nearly 60,000 deaths per year in the U.S. alone.
The application of this test for patients with colon and rectal cancer, however, may only be the beginning. Irinotecan also is being tested and used for other GI cancers as well as lung and breast carcinoma.
The Department of Laboratory Medicine and Pathology at Mayo Clinic maintains an active diagnostic test development program. These activities also incorporate discoveries made elsewhere, such as the UGT1A1 patents from the University of Chicago. Mayo Clinic offers these proven diagnostic technologies to more than 5,000 health care institutions around the world through MML.
Mayo acquired an exclusive license to the UGT1A1 technology from the University of Chicago, which includes the right to sub-license the test, and will actively pursue agreements with other academic medical centers, laboratories, diagnostic test companies and pharmaceutical companies to ensure that patients everywhere have access to this important screening test. Mayo recently sub-licensed the rights under the University of Chicago patent to Third Wave Technologies.
Revenue from MML testing and technology licensing is used to support medical education and research at Mayo Clinic. Camptosar® is a Pfizer product.