By Ben Butkus
Spartan Bioscience has completed a validation and proof-of-concept study in Canada showing the ability of its flagship point-of-care DNA testing system to identify patients carrying the CYP2C19*2 mutation at the time of cardiac catheterization and help guide appropriate anti-platelet therapy.
The company expects the study's results to generate additional sales of the platform, called the Spartan RX, among cardiologists in countries recognizing CE Marking, which Spartan obtained late last year.
Spartan is also betting that the results of the study will drum up interest in the platform from US physicians ahead of receiving 510(k) clearance in the US — a goal that the company believes it can achieve by the end of 2012, a year later than it originally hoped, CEO Larry D'Andrea told PCR Insider this week.
In the meantime, the company is also initiating a $7.8 million R&D project in collaboration with Canadian universities and industry players to develop a version of the platform for food and water safety applications, D'Andrea said.
Spartan, based in Ottawa, Ontario, launched the Spartan RX platform for research use only in August 2010 (PCR Insider, 8/12/2010). It is a lightweight, portable, benchtop device that integrates sample prep and non-batched PCR analysis, and only requires the user to collect a buccal swab, place it in the analysis tube, and run the machine.
The first Spartan RX assay is designed to test patients for the CYP2C19*2 mutation, which is carried by approximately 30 percent of the world's population and has been associated with poor response to the anti-platelet therapy Plavix (clopidogrel) following a cardiac stent insertion.
Spartan has been underscoring the platform's ease of use, claiming that personnel can be trained to use the device in minutes; as well as its time to result, about an hour, compared to a day or more for decentralized laboratory testing.
In December Spartan RX received a CE Mark for in vitro diagnostic use and the company began selling the platform throughout Europe and in non-European countries recognizing the CE Mark (PCR Insider, 12/23/2010).
In the meantime, eyeing the US and Canadian markets, Spartan initiated the "Reassessment of Anti-platelet Therapy Using an Individualized Strategy Based on Genetic Evaluation," or Rapid Gene, study, in Canada. Led by Derek So, an interventional cardiologist at the University of Ottawa Heart Institute, the study enrolled 200 patients who were being treated with cardiac stenting for an acute coronary syndrome or stable angina.
Patients were randomized to a treatment strategy of point-of-care genotyping with the Spartan RX and Eli Lilly's Effient (prasugrel) for CYP2C19*2 carriers; or standard therapy with Plavix, marketed by Sanofi-Aventis and Bristol-Myers Squibb. Nurses that received 30 minutes of training but had no prior laboratory training administered the Spartan RX test.
According to Spartan, the test had a sensitivity of 100 percent and specificity of 99.4 percent compared with DNA sequencing. In addition, for CYP2C19*2 carriers, treatment with prasugrel completely eliminated high on-treatment platelet reactivity, or HPR. In contrast, 30.4 percent of carriers receiving clopidogrel experienced HPR at one week.
Spartan presented data from the trial at the Transcatheter Cardiovascular Therapeutics conference, held last week in San Francisco. According to the company, the study is the first randomized, prospective clinical trial to demonstrate the utility of point-of-care DNA testing for personalized medicine.
According to D'Andrea, the researchers who performed the study will likely submit it for publication in a peer-reviewed journal, and Spartan is hoping the results of the trial will spur additional sales of the Spartan RX in countries recognizing the CE Mark, where Spartan has already placed several platforms.
"This definitely helps with the cardiologists in terms of helping to build the story on the clinical efficacy of the test … [and] what they can do with the results of the test," D'Andrea said.
One of the first Spartan RX CYP2C19*2 users, Alan Rayner, chief clinical perfusion scientist at London Bridge Hospital in the UK, told PCR Insider in an e-mail that his group started using an individualized approach to anti-platelet therapy prescription two years ago.
According to Rayner, the Spartan RX platform represented "a significant advance" in the individualized program already in place at the hospital, which is based on the Multiplate functional analyzer for whole blood analysis from Germany's Verum Diagnostica.
Rayner noted that since most of the literature points to the occurrence of major cardiac events in the first 48 hours following stent placement in patients who do not respond to anti-platelet therapy, "we feel that it is essential to have an understanding of their genotype and functional platelet activity within this timeframe."
Rayner said that his group routinely assesses all patients undergoing percutaneous coronary intervention on aspirin and clopidogrel for effect using the Multiplate analyzer. "Patients who are non-responders to clopidogrel have genetic analysis using the Spartan RX to identify *2 status," he said. "In this way we are able to determine whether they would benefit from an alternative drug, most frequently prasugrel, with evidence."
The combined Multiplate/Spartan RX program has been in place for about four months, during which time the group has assessed more than 50 patients. About 30 percent of those patients screened with Spartan RX are CYP2C19*2 carriers, and about 40 percent of patients screened for functional activity are non-responders to clopidogrel, he said.
"Traditional genetic analysis through specialized laboratories is available," Rayner noted, but the time taken to obtain results – often up to two weeks – as well as the significantly higher cost makes this option unsuitable for rapid individual patient assessment. "We are able to obtain functional and genotype data within an hour, at the point of care, which enables our cardiologists to make decisions immediately," he said.
In addition to pursuing new sales overseas, Spartan has turned its attention toward achieving US Food and Drug Administration approval for the Spartan RX, which the company had originally hoped to obtain by the third quarter of this year.
"FDA has a different requirement" than the results of the Rapid Gene study, D'Andrea said. "It's much more concerned with tests that prove it works in different circumstances [such as] in the presence of contaminating substances.
"The requirements are … probably a little more than we expected," he added. "The FDA process is not simple or easy to understand. And we also didn't start as soon as we would have liked to." As such, the company is now targeting the end of 2012 for 510(k) clearance, D'Andrea said. The company is eyeing a similar timeline for regulatory approval in Canada.
D'Andrea claimed, however, that the positive results from the Rapid Gene study are already generating interest among cardiologists in North America. The company attended the American Heart Association annual meeting this week after it presented at the TCT meeting last week, and D'Andrea said that at both events "we met cardiologists from the US that said, 'Tell me as soon as it's available because I'd love to start using it.' Right now we can just show them the European device and say we're [planning] to be FDA approved next year."
Concurrently, Spartan is spearheading a two-and-a-half-year, $7.8 million R&D project to develop a low-cost, sample-to-result DNA testing system for pathogen identification in food and water safety testing.
According to D'Andrea, the company and its collaborators will develop tests for Listera monocytogenes, Escherichia coli, and Salmonella species. Spartan envisions that this testing platform "will dramatically reduce the time it takes to get a result," D'Andrea said. For example, a Listeria test that currently takes four to seven days with traditional methods will take only two to four hours on the Spartan platform.
The temptation exists to adapt the Spartan RX platform for other applications in pharmacogenomics, oncology, and infectious disease, but Spartan plans to focus in the near term primarily on commercializing the CYP2C19*2 test in North America and exploring the food and water testing market.
"We have requests all the time from people asking if we can test for this or that … so there is a pretty healthy list of potential development projects," D'Andrea said. "But at the moment we are really focused on those two."
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