Originally Published IVD Technology
Originally Published IVD Technology April 2003
INDUSTRY NEWSDNA chips enter the clinical market
With a $70 million up-front payment, Roche (Basel, Switzerland) has licensed Affymetrix’s (Santa Clara, CA) GeneChip DNA microarray technology. The agreement has given Roche nonexclusive access to Affymetrix’s array and instrument technologies for up to 18 years. This alliance will be used to develop and commercialize microarrays with both diagnostic and therapeutic applications for a wide range of disease areas. Roche will brand the new platform AmpliChip.
The first product to come out of the Roche-Affymetrix alliance is a chip that characterizes a patient’s ability to metabolize certain drugs, based on the patient’s genetic profile. The microarray detects mutations in genes 2D6 and 2C19 on cytochrome P450. These genes affect the ability of the liver to metabolize several classes of drugs that include more than 25% of the drugs available on the market.
Pharmaceutical manufacturers have examined CYP450 variations for years in an effort to determine the safety of drugs in development. However, the release of this chip will mark the first time CYP450 testing has entered the clinical diagnostics market.
Although Roche only recently purchased its license to this technology, it has been working with Affymetrix on CYP450 for the past three years. Roche has made several improvements to Affymetrix’s original version of the CYP450 chip, thereby doubling the number of gene variations the chip can detect. Among these improvements are the chip’s ability to detect deletions and duplications of the CYP2D6 gene as well as several allelic variations unique to African and Asian populations.
The metabolic analyses performed by the chip will eventually offer practitioners a tool to aid them in prescribing more-effective dosages of medication. The test will enable physicians to categorize a patient into one of four metabolic types. Knowledge of a person’s metabolic genotype can help prevent adverse reactions to prescribed drugs or to incorrect dosages.
Melinda Baker, communications manager for Roche Diagnostics (Pleasanton, CA) says that this can be particularly useful in the prescription of drugs for depression and other psychiatric conditions. “Psychiatric drugs are notoriously difficult to effectively prescribe, because it can take a long time to get a person to the correct dose level,” she says. “Currently, there is a lot of trial and error in this area. Understanding a person’s genotype can get them the right dosage faster and help them avoid a class of drugs to which they might suffer adverse reactions.”
The product will include both a set of reagents and a microarray, and will be released in the second quarter of 2003. Initially, the technology will be restricted to use in reference laboratories, to which it will be marketed as an analyte-specific reagent (ASR) set. However, Roche expects that within the next 3–5 years, it will develop the technology into a fully automated system that can be marketed as a certified in vitro diagnostic. The company hopes to eventually bring the test closer to the patient for use in clinical laboratories or even at the point of care.
Thomas Metcalfe, senior vice president for genomics business at Roche Diagnostics, says that several obstacles must be overcome before the test can be developed to its full potential. “We are facing technical challenges because there are very many steps that must be integrated into an easy-to-use platform,” he says. “The time between when a test is ordered and the results are delivered will have to be shortened. Currently, results from this type of test can take from 4 days to a week to deliver. We are also facing market adoption challenges, including educating people about how the technology works and what its benefits might be.”
The technology is expected to produce a profit that is well worth the requisite investment of time and effort. Metcalfe projects that for the CYP450 microarray alone, the annual revenue could be $60 million in 4–5 years. However, he believes that the CYP450 chip will be only one of several pharmacogenomic tests for the platform. Metcalfe expects that, within the next decade, the market for diagnostic applications for DNA microarrays as a whole will reach $3 billion annually.
Though a few similar metabolic tests do exist, they are often very narrow in scope, whereas the AmpliChip technology promises a wide range of applications. For example, the Thiopurine S-methyltransferase (TPMT) test is used to test a patient’s metabolic type prior to his or her use of azathiprine, a chemotherapy drug.
Metcalfe expects that the technology will have a variety of applications including helping direct a course of therapy and
diagnostics for oncology, common complex diseases including osteoporosis and cardiovascular diseases, metabolic disorders, and infectious diseases.
Until the platform is developed into a certified diagnostic, however, the company cannot make any claims about its performance characteristics. The fact that reference laboratories will be using home-brew reagents alongside the AmpliChip reagents means that, while the platform is sold as an ASR, test results may vary between laboratories.
On the whole, news of the test’s upcoming release seems to have been warmly welcomed by the diagnostic industry, which has been waiting for years for the technology to reach the clinical market. “I am very intrigued and excited by this announcement,” says John Tonkinson, PhD, senior scientist at Schleicher and Schuell BioScience Inc. (Keene, NH).
“Pharmacogenomics is the logical place for microarray technology to be introduced into the clinical market. I think the AmpliChip, if successful, will help bridge the gap between interesting research tools and useful clinical tools.”
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