By Ben Butkus
Quest Diagnostics subsidiary Focus Diagnostics is developing a CYP2C19 genotyping test to aid physicians in predicting a patient’s response to clopidogrel, sold by Bristol-Myers Squibb under the brand name Plavix, a Quest spokesperson said this week.
In addition, Focus and Quest are collaborating with clinical scientists from Scripps Translational Science Institute and Scripps Health to develop the test, which could eventually help clinicians personalize treatment based on a patient’s CYP2C19 genotype in less than an hour.
Details about the test’s development are still under wraps, for the most part, due to the early nature of the project.
However, in an e-mail to PCR Insider, a Quest spokesperson confirmed that “Focus Diagnostics, the infectious disease products business of Quest Diagnostics, is in the early stages of developing a Simplexa-branded molecular test for use on the 3M Integrated Cycler for aiding the prediction of response to clopidogrel.”
Focus’ Simplexa tests, the spokesperson added, “are designed to empower hospital, urgent care clinics, and other labs to perform highly advanced molecular testing nearer to their patients, for faster reporting of results.”
In 2009, Focus inked an exclusive distribution agreement with 3M that would couple molecular diagnostic kits developed by Focus with 3M’s Integrated Cycler platform under the Simplexa name and target customers at hospital laboratories.
The 3M Integrated Cycler is a benchtop instrument that can process up to 96 samples in a 30- to 75-minute run depending on the analyte. The reduced footprint of the instrument is due to a disc-shaped consumable cartridge — as opposed to the more standard plate-based thermal cycler design — that promotes extremely fast heat transfer.
There are currently two Simplexa tests cleared by the US Food and Drug Administration. In May 2010, the Simplexa Influenza A H1N1 (2009) test on the 3M Integrated Cycler was the first commercial RT-PCR test to receive FDA clearance to detect and differentiate the 2009 H1N1 influenza and other influenza A viruses. The test had previously received emergency use authorization in October 2009.
In December, the FDA cleared the Simplexa Flu A/B RSV test on the 3M Integrated Cycler to aid in detecting and differentiating influenza A, influenza B and respiratory syncytial virus infections.
Focus has other infectious disease tests under development for use on the Integrated Cycler; and Quest currently offers a PCR-based clopidogrel response test, the AccuType CP. However, a molecular genotyping assay for clopidogrel response would be the first non-infectious disease test for the Integrated Cycler.
The FDA last year added a “black box” warning to the label for Plavix, notifying healthcare providers that patients with diminished CYP2C19 function are at greater risk of cardiovascular adverse events after an acute coronary syndrome or percutaneous coronary intervention than normal metabolizers of Plavix. The agency does not require genetic testing prior to Plavix administration, however, and has not approved any tests for that indication.
Late last year the agency cleared AutoGenomics’ Infiniti CYP2C19 Assay, but the test’s label makes no mention of its use as a pharmacogenetic test to administer Plavix.
Aiding in the development of the Focus Simplexa test are Eric Topol, director of STSI and chief academic officer at Scripps Health; and Matthew Price, an associate professor at STSI and director of the cardiac catheterization laboratory at the Scripps Clinic.
“Quest Diagnostics has advisory relationships with elite medical experts who aid our diagnostics research and development,” the spokesperson said. “Drs. Topol and Price of Scripps are two of our academic advisors, and are assisting our research of a near-patient Simplexa genetic clopidogrel-response test.” The spokesperson also noted that as a client of Quest’s, Scripps Health was the first health system in the US to offer genetic clopidogrel response testing as part of its care for elective coronary stent patients, using the AccuType CP CYP2C19 test.
According to Price, however, the partners are developing the Simplexa test with the aim of addressing the unmet medical need of quickly and easily providing clinicians, in most cases interventional cardiologists, information about a patient’s CYP2C19 genotype, and thus sensitivity to Plavix, in the acute care setting.
“It’s become quite clear that there is a risk associated with carrying a certain CYP2C19 genotype and outcomes after stent implantation in patients treated with clopidogrel,” Price told PCR Insider this week.
Despite this, “and despite the box warning by the FDA and the availability of genotyping tests, the adoption of CYP2C19 genotyping has not been all that great among practitioners,” Price said.
Price said that part of the reason for this is that currently available tests, including AccuType, have a much longer turnaround time — in some cases days — than is desirable in the case of a patient presenting with a heart attack or chest pain, or receiving elective stent treatment before discharge from the hospital.
“The issue is that stent implantation, and the doctors who do them, work in the acute care setting,” Price said. “They make their decisions right away … and it would be best if they could make the appropriate individualized anti-platelet plan at the actionable moment.”
Another issue is that testing is “fairly arduous, in that you need technical training and infrastructure … and many clinical labs aren’t equipped to do that,” Price said. “So what happens is you get a genotype, you need to get a sample and send it out to a central lab, which takes anywhere from 24 hours to five or seven days, depending on batching of patient samples.”
Price said that the quicker a test can be completed, the better. “The question is: how quick does it have to be? Right now we’re talking about days. If we can get that to hours, it’s much more attractive,” he said. Lastly, any point-of-care test should not need batch sampling, which can further delay turnaround time.
Other fast point-of-care tests exist, such as Nanosphere’s Verigene, which can provide results in about four hours without batching. But a 30- to 40-minute test, which may be possible on the 3M Integrated Cycler, may open up an additional layer of fast, individualized care.
“The guidelines in the US for someone who’s presenting with what is called an ST elevation myocardial infarction is to get from the door of the emergency room to a balloon in the artery … in 60 to 90 minutes,” Price said. “So once you’re at 30 to 40 minutes for a test, you’re talking about really being able to integrate something in the acute emergency care of a patient.”
Canadian molecular diagnostics firm Spartan Bioscience also offers a CYP2C19 molecular test on its Spartan Rx PCR-based point-of-care testing platform. The test, which has received a CE Mark for in vitro diagnostic use, and the company claims that it can be performed by a relatively unskilled healthcare worker or technician at the point of care in about an hour (PCR Insider, 12/23/11).
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