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Stanford Adds CYP2C19 Rapid Test to Genomics Menu, Plans Future PGx Expansion

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NEW YORK – Stanford Medical Center has added rapid PCR-based testing for CYP2C19 to its larger menu of genomic and molecular tests, in line with growing data on its value in treating patients with transient ischemic attacks (TIA) or small strokes.

Using a platform called the Genomadix Cube, which was cleared by the US Food and Drug Administration last year alongside a paired CYP2C19 assay, Stanford's genomics lab can now provide results for ordering neurologists within 24 hours, with the test itself taking approximately 45 minutes to run.

While CYP2C19 testing has faced some resistance from clinicians in other settings based on skepticism regarding clinical utility, Stanford stroke biologist and neurology professor Neil Schwartz said that the benefit to patients in this setting, especially with new rapid and point-of-care testing options, seems clearer.

"What's emerged over the last decade or two is that the addition of Plavix (clopidogrel) to aspirin in patients presenting with TIA is really beneficial," Schwartz said.

He added that it has become standard for the center to put patients on a dual antiplatelet treatment, "but it turns out that a not-insignificant number of people may be Plavix non-responders because they have a 2C19 polymorphism such that Plavix is not converted into the active drug."

The CHANCE-2 study, which was performed in China and published in 2021 in the New England Journal of Medicine, confirmed this, finding that the risk of stroke at 90 days was lower, albeit modestly, with the alternative blood thinner ticagrelor than with clopidogrel in 2C19 variant carriers.

Importantly, the risk of severe or moderate bleeding did not differ between the study's two treatment groups, as bleeding risk has been somewhat of a barrier to test adoption in the cardiology community.

Strokes are a leading cause of adult disability in the US, Schwartz said, so the ability to prevent them in patients presenting with TIA is crucial.

Stuart Scott, director of Stanford's Clinical Genomics Laboratory, said that Schwartz first proposed instituting CYP2C19 testing almost two years ago.

"It took us some time to think through the trends and the platform, but that ultimately led us to Genomadix last summer when the FDA approved their instrument," Scott said.

Although Stanford's neurologists have had access to genetic testing prior to this, ordering a 2C19 test from an outside lab could take weeks.

"That's not particularly helpful because this high-risk period is a few days to a few weeks, so we really would like to get that result within hours to help make this decision," said Schwartz.

He added that it was "a lot of work by many folks" to get the Genomadix test rolled out. The lab began clinical testing early this month, with physicians ordering it in two places in the Stanford Medical system. The first is an observation unit in the emergency room, which is where a lot of TIA patients are typically housed who don't need to be admitted.

The other place testing can be ordered is on the actual neurology floor. Ultimately the goal is to have in-house testing, and have it be available in the outpatient neurology stroke clinic, as well as in other areas of practice like cardiology, where its use in patients undergoing stent placement could also prevent future strokes, Schwartz said.

Scott said that when Schwartz approached him about CYP2C19, he and his laboratory colleagues had already been working on an innovative comprehensive long-read sequencing panel for broader pharmacogenomics testing, which they hope to launch by the end of the year.

But in the meantime, the lab began to look for a rapid alternative. "We didn't have a platform that could meet their turnaround time needs at the time," Scott said. "The best we could do was about a week."

The search for a new instrument brought the group to Genomadix, which Scott had worked with previously when the company was called Spartan Bioscience.

"We found out that their device was FDA-cleared about a year ago and so that made the decision pretty easy to go with them," Scott said.

The team brought the technology into Stanford's genomics lab last fall and validated the CYP2C19 assay over the winter. After ironing out workflow and logistics, the testing is now live.

Although testing is currently housed in the genomics lab, Scott said that the Genomadix device is designed and cleared for point-of-care testing, so in the future, the medical center may change that strategy.

"Because this was so brand new as a whole kind of program and implementation, we thought it would be best to have the Cubes in the genomics lab first and then gradually move it over to the main lab on campus and then potentially to [the] point of care," he said.

Test uptake has been in line with what Schwartz and Scott had expected thus far, with about four to five tests being run per week. The medical center sees approximately one or two TIA cases every day, and Schwartz said that the reason not all patients might get a test ordered is complex.

"Some of them may be on different medications, and Plavix is not even going to be an option. Some might not turn out to be actual TIAs, and it may be that it just gets missed," he explained.

The hospital uses Epic Systems for its patient records and test requisitions, but Schwartz said that unlike some other academic health centers that have implemented prompt systems to remind their doctors to consider CYP2C19, Stanford has decided not to actively tag patients with TIA as needing a test in its own EHR system.

"It's difficult because the clinicians in general who are placing orders … can get annoyed by these things that pop up saying you have to do this or you can't go further," said Schwartz. "I can envision a future where we're smarter in that way, but at the moment, we are just relying on the experts to remember to think about that," he added.

Schwartz and colleagues are not alone in embracing CYP2C19 testing in the setting of stroke care. The UK National Institute for Health and Care Excellence (NICE) said last May that it is now recommending genetic testing for patients with ischemic stroke or transient ischemic attack prior to prescribing clopidogrel.

Mayo Clinic has also been working with Genomadix but has not made any announcements about using the Cube system for CYP2C19 testing.

Meanwhile, other competing rapid point-of-care platforms may also soon be available if demand grows in the clinic. One example is Genedrive's CYP2C19 System, which received UK Conformity Assessed-marking registration last fall, allowing it to begin necessary research to support CE-marking by the end of this year.