By Turna Ray
Vying to break into the point-of-care testing market to guide anti-platelet treatment in cardiac patients, at least two molecular diagnostics companies are studying the utility of their rapid tests in clinical trials.
Spartan Bioscience announced this week that researchers at the University of Ottawa Heart Institute are using its Spartan RX point-of-care testing system to gauge CYP2C19 mutations that may impair cardiac patients' response to Bristol-Myers Squibb's anti-clotting drug Plavix.
Separately, Nanosphere's investigational Verigene point-of-care CYP219 test is being used by the Center for Thrombosis Research at Sinai Hospital of Baltimore in a study to identify which patients are at risk for a cardiac event after coronary stenting. The primary outcome of the study is to demonstrate a 30 percent relative risk reduction in post-percutaneous coronary intervention ischemic event occurrence with personalized, guided antiplatelet treatment compared to standard treatment
Spartan, which this week launched the Spartan RX CYP2C19 test for research use only, said that the University of Ottawa Heart Institute is using the test in a prospective, randomized controlled clinical trial. The study, called Rapid Gene, is investigating whether treatment with Effient, developed by Eli Lilly and Daiichi Sankyo, can reduce cardiac adverse events for CYP2C19*2 carriers who would not respond to Plavix. Data from this trial will be part of Spartan's submission to regulatory authorities for marketing approval.
Effient is the major competitor to Plavix, which is slated to lose patent protection in 2012. As drugmakers compete to grasp a share of the large market for anti-clotting medications, opportunities are ripe for diagnostic developers marketing tests that will help doctors determine whether Effient or Plavix will be the most effective treatment for their patients. However, CYP2C19 tests that are currently on the market have a turnaround time from a day to up to a week, which means that genetic testing may not be useful for guiding anti-platelet treatments in the acute setting. As such, point-of-care CYP2C19 tests promise to capture this untapped market.
The anti-clotting drug market is estimated to reach $12 billion by 2021, according to market research by Barclays. In line with this growth, "the long-term trend for DNA testing is to move from the central lab to point-of-care," said Spartan Founder Paul Lem, in a statement.
Spartan isn't the only company eyeing the CYP2C19 point-of-care testing market, however.
For example, Nanosphere's investigational CYP2C19 test is being used by Sinai Hospital's Paul Gurbel in a 1,500-patient study called “Thrombocyte Activity Reassessment and Genotyping for Percutaneous Coronary Interventions," or TARGET-PCI, which began on July 15 and is slated for completion in 2012.
These testing systems are intended to help cardiologists quickly identify patients with impaired metabolism to Plavix, which would result in major cardiac events. The CYP2C19*2 mutation, found in 30 percent of the general population, confers a 11.7 percent absolute risk of death, stroke, or heart attack in patients treated with Plavix after a stent procedure, versus 8.3 percent risk in noncarriers of the allele.
According to Spartan, its point-of-care test returns test results in one hour, an improvement over the one to seven days it usually takes a central lab to return test results. The company said that its testing system is a "fully integrated DNA collection, extraction, and analysis platform," and the test's interface is designed so it "can be operated by nurses and other non-technical users."
In addition to Nanosphere's investigational use test that gauges a large number of CYP2C19 SNPs, the company is currently developing a CYP2C19 test for clinical use that gauges three SNPs. Earlier this month, Nanosphere CEO William Moffitt said during an earnings call that the company was "about to file a PMA with the FDA for [its] 2C19 assay used to guide anti-platelet therapy using … Plavix."
Upon FDA approval of the Verigene test, Gurbel and his team "plan to make point-of-care genetic and platelet function testing available to all cardiac patients at the Heart Center at Sinai," the hospital said in a statement. According to Gurbel, TARGET-PCI aims to determine whether the Verigene CYP2C19 test can generate results in a matter of hours at the point of care and positively impact patient outcomes.
TARGET-PCI is a prospective, single-center, randomized trial involving patients with ischemic heart disease undergoing PCI with stent placement and no contraindication to prolonged dual antiplatelet therapy for a year or more. Study participants will be randomized to either the guided antiplatelet therapy arm or standard therapy arm and undergo genetic testing, antiplatelet adjustment, and clinical follow-up for one year. Study participants on chronic Plavix or Effient therapy for two weeks or more will be guided by the VerifyNow P2Y12 assay, whereas treatment for Plavix-naïve patients will be guided by Verigene CYP2C19 genotyping assay.
Separately, Medco Research Institute has also launched a head-to-head trial of Plavix and Effient measuring the impact of genes in patient response to these drugs (PGx Reporter 10/21/09). That study will examine whether the 70 percent to 75 percent of patients who are "extensive metabolizers" of Plavix have similar outcomes to patients taking Effient.
The US Food and Drug Administration this year instated a black box warning on the label for Plavix, to caution healthcare providers that patients with diminished CYP2C19 function, or poor metabolizers of the drug, are at greater risk of cardiovascular adverse events after an acute coronary syndrome or percutaneous coronary intervention than normal metabolizers of Plavix (PGx Reporter 03/17/10).
In announcing the black box warning, FDA officials acknowledged that depending on the urgency of their patients' medical condition, doctors can't always wait for genetic test results. According to labeling language, it is up to doctors to determine when they should genetically test patients before Plavix administration, or if they should see how patients react on a particular dose of Plavix and decide whether to switch to another drug depending on the outcome.