Testing behemoth Laboratory Corporation of America is validating Roche Molecular Diagnostics' AmpliChip CYP450 chip as it and rival Quest Diagnostics move toward offering diagnostic testing services with the microarray-based system.
"We do a lot of evaluations, and we do a fair number of validations," said Marcia Eisenberg, LabCorp's vice president overseeing research and development in molecular diagnostics. "When you're committing the time and effort and resources to a validation, you're doing that with the hope that at the conclusion it will be something you can offer to physicians for their patients."
Although the AmpliChip CYP450 was the first microarray-based product to gain FDA clearance as a diagnostic device, Roche's chip still has to gain a customer base, and aside from the reliability implied by FDA approval, the chip does not offer LabCorp customers new tests that they couldn't get through PCR testing, Eisenberg said. However, the chip's impending adoption by the biggest labs on the block probably signals that there are some in the diagnostics industry feel that the market for CYP450 testing • array-based testing included • has the potential to grow.
"This is not cholesterol testing or cystic fibrosis testing."
AmpliChip is still not yet on the market, but when it is, it will have to contend with the same forces that dampened demand for LabCorp's PCR-based CYP450 tests. The company has been offering PCR-based CYP450 2D6 testing as a diagnostic under Clinical Laboratory Improvement Amendments rules since spring, and plans to begin offering 2C19 testing as well. One difficulty the chip will face is that physicians remain uninformed about how to use CYP450 testing in general, partly because they lack educational material and other information about the microarray and the genes it tests, said Eisenberg. Until AmpliChip's January approval, the lack of an FDA-approved CYP450-testing method and a lack of interest on the part of pharma contributed to slow demand for the service, she said.
"I don't think we are looking for this to grow to become a routine high-volume diagnostic test," said Gary Samuels, a spokesperson for Quest, the second-largest lab-testing company in the United States. "This is not cholesterol testing or cystic fibrosis testing." Quest conducted the validation studies that Roche submitted to the FDA for the AmpliChip CYP450's approval, and the company will begin offering testing with the chip "later this year," he said.
The introduction of AmpliChip CYP450 testing at the two major diagnostic-laboratory firms may play a similar role as the chip's clearance by the FDA late last year: as a harbinger of things to come. "We see this technology playing a growing role in our area of the healthcare world," Samuels said. "This is an important technology platform that is kind of in its infancy at the moment."
Indeed, the whole field of pharmacogenomics is in its infancy. LabCorp has offered PCR-based CYP450 testing to pharma for clinical trials, but it only recently made the service available for diagnostics, said Eisenberg. "And so, the test is being ordered, and there has been some interest in it both clinically and for clinical trials," she said. Recent guidance documents have helped steer pharma in the direction of CYP450, "and so, I think you'll continue to see increased demand for the testing because they're being asked to be interested," she said.
Other factors will also lift demand, said Eisenberg. LabCorp is "actively in a phase right now where we're educating physicians as to the use of P450 testing for the treatment of their patients," she said. The technique's recent popularity might have an effect too. "The data that's come out for [CYP450] 2C9 and warfarin • those kinds of things will continue to increase demand, because that's a message that physicians will hear," she said.
"I think Roche is capable of making a market," Paul Billings, LabCorp's senior geneticist and vice president for biotechnology and healthcare strategy, told Pharmacogenomics Reporter. "I know for a fact that Roche is engaged in pilots and clinical trial work that will presumably sharpen the indications for P450 use, and the uncertainty … amongst practitioners about how to use it will clarify over time," he said.
An expansion of demand is one thing, but with Roche's limited initial market • largely practitioners in psychiatry and cardiology • requests for the test might not reach the level of an explosion. When asked in January about demand for CYP450 testing, Billings characterized it as fairly low, and said that a health-economics assessment might be used to determine where the test fits into LabCorp.
"We think that there's an argument for playing a role in some doctors' first- or second-line choice of medications, or for its use in warfarin dosing or understanding who's relatively warfarin resistant," said Billings this week.
At least 41 drugs are CYP2D6 substrates, according to a website developed by David Flockhart, chief of the division of clinical pharmacology at the Indiana University School of Medicine. At least 34 drugs inhibit the enzyme and two are inducers, according to the site.
Very few people are willing to estimate the size of the market for CYP450 microarrays. Jurilab's DrugMet microarray is similar to Roche's CYP450 AmpliChip, but "it's a little bit broader in content," Jurilab CEO Kari Paukkeri told Pharmacogenomics Reporter. "The same customers are interested," he said, adding that those customers are largely satisfied with the research-use-only strictures of the not-yet-cleared DrugMet, because "there is no true clinical market for the product." The market for these diagnostics won't really pick up until the FDA requires the use of such a test on the label of a drug, Paukkeri said.
ParAllele's Megallele D-Met assay, which Affymetrix will soon own when its acquisition of ParAllele is complete in the third quarter, can be used in as many as 1 million genotyping assays in the United States annually, based on the number and size of clinical trials, Aaron Solomon, vice president of business development at ParAllele, said in March. Solomon said Parallele had not developed an estimate of the clinical market.
Tm Bioscience sells about 300,000 or 400,000 of its bead-based CYP450 tests annually, although the CYP450 market should "take off significantly" as AmpliChip settles in and competitors achieve IVD approval, said CEO Greg Hines in January. The company currently sells its CYP450 assays to the Mayo Clinic, the University of Louisville, and "four of the top six" labs in the United States, he said.
• Chris Womack ([email protected])