Marshfield Clinic Research Team Uses Affymetrix DMET Solution to Discover Genetic Variant Affecting Warfarin Metabolism in Patients

Results to Help Improve Drug Dosing Dilemma and Reduce Risks of Adverse Reactions

SANTA CLARA, Calif. & MARSHFIELD, Wis.–(BUSINESS WIRE)–Affymetrix Inc. (Nasdaq:AFFX) and Marshfield Clinic today announced that researchers at Marshfield Clinic used the Affymetrix Drug Metabolizing Enzymes and Transporters (DMET) solution to discover a genetic variation associated with an individuals response to the drug warfarin.

The study, CYP4F2 genetic variant alters required warfarin dose, was published this week by Blood Online. The results of the study could help reduce much of the serious adverse events caused by incorrect warfarin dosage and enable doctors to treat patients with a more effective, personalized form of medicine.

The team of scientists, led by Michael D. Caldwell, M.D., Ph.D., of Marshfield Clinic, discovered a genetic variation in a gene called CYP450 4F2 (CYP4F2) that explains approximately 8 percent of a patients variable response to warfarin. The discovery was made possible because of the DMET solution, which is the industrys most comprehensive method for assaying the genetics of drug metabolism. Marshfield has already begun testing the result in a prospective Phase III clinical trial expected to be completed by the end of 2008 and funded by the Agency for Healthcare Research and Quality (AHRQ).

This discovery should enable us to better predict a stable therapeutic dose and hopefully reduce the overall complications of warfarin therapy, said Dr. Caldwell. Understanding the factors and genetic variations that affect the metabolization of drugs gives doctors a much more accurate idea of how best to treat patients. The nations entire healthcare system can benefit from these types of advances.

In August 2007, the U.S. Food and Drug Administration (FDA) announced that they would be updating the labeling of warfarin with known valid markers in the CYP2C9 and VKORC1 genes to provide information on how an individuals genetics may impact their response to the drug. The use of warfarin is complicated due to its small therapeutic index window of dosage. If a dose is too high, there is a risk of bleeding; if a dose is too low, the drug will be ineffective and there may be a risk of clotting. The optimum dosage is affected by factors such as genetics, age, body mass index and gender.

Marshfield Clinic has one of the worlds largest and best characterized patient populations for warfarin treatment and we are thrilled to collaborate with them to help solve this dosing problem, said Maneesh Jain, senior director of marketing at Affymetrix. This study is an example of the power and ability of our DMET solution. Clinical researchers are now able to take a comprehensive look at all of the drug metabolism biomarkers, which will enable clinicians and pharmaceutical scientists to develop safer and more effective treatments.

In January, Affymetrix launched its DMET Early Access solution, an updated version of the assay used in the Marshfield warfarin study. Pharmaceutical customers are using the DMET solution to better understand pharmacokinetics, the study of the bodily absorption, distribution, metabolism and excretion (ADME) of drugs. DMET is the only product available with comprehensive coverage of all ADME drug metabolism biomarkers. It profiles more than 1,069 drug metabolism biomarkers, including 172 core genetic markers. Data is automatically interpreted into a common format that can be integrated into clinical trial workflows. The information enables researchers to make more informed drug-development decisions, which in turn significantly streamlines the drug-development process and, therefore, the time to market.

For more information the Affymetrix DMET Early Access Solution, please visit:

About Marshfield Clinic

The Marshfield Clinic system provides patient care, research and education with more than 40 locations in northern, central and western Wisconsin, making it one of the largest comprehensive medical systems in the United States. For more information about Marshfield Clinic, visit:

About Affymetrix

Affymetrix GeneChip® microarray technology is the industry-standard tool for analyzing complex genetic information. After inventing microarray technology in the late 1980s, Affymetrix scientists have been dedicated to developing innovative products that provide researchers with a more complete view of the genome. These products continue to accelerate genetic research and enable scientists to develop diagnostics and tailor treatments for individual patients by identifying and measuring the genetic information associated with complex diseases.

Today, Affymetrix technology is used by the worlds top pharmaceutical, diagnostic and biotechnology companies, as well as leading academic, government and not-for-profit research institutes. More than 1,600 systems have been shipped around the world and more than 10,500 peer-reviewed papers have been published using the technology.

Affymetrix is headquartered in Santa Clara, Calif., and has manufacturing facilities in Sacramento, Calif., Cleveland, Ohio, and Singapore. The company has about 1,100 employees worldwide and maintains sales and distribution operations across Europe and Asia. For more information about Affymetrix, please visit:

Forward-looking Statements

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