diaDexus (South San Francisco, California) is going for a second use for its PLAC test, which is now used to predict the risk of coronary heart disease in chronic patients. The company recently submitted a 510(k) premarket notification to the FDA seeking marketing clearance for the PLAC test as a diagnostic to help predict the risk of stroke.
The PLAC test is a blood test that measures an enzyme in the blood called lipoprotein-associated phopholipase A2 (Lp-PLA2). The company said that "large population studies" demonstrated that elevated Lp-PLA2 is associated with an increased risk of ischemic stroke.
Mohan Iyer, vice president of business development for diaDexus, told Medical Device Daily that the company hopes to get marketing clearance from the FDA by mid-year or earlier.
"This is not an entirely new submission," Iyer said. "It's . . . based on the coronary heart disease submission to a large extent, and our hope is that many of the questions that the FDA might ask have already been cleared in the original submission."
diaDexus secured approval of its PLAC test in coronary heart disease in July 2003 (MDD, July 23, 2003). It was the company's first FDA-approved product.
According to the American Heart Association (AHA; Dallas), stroke is the third-leading cause of death in the U.S. and a leading cause of severe, long-term disability. About 700,000 Americans will suffer from a stroke this year and 500,000 of those will be first attacks. Risk factors stroke include high blood pressure, smoking, diabetes or other heart disease, and obesity, as well as heredity and race.
For use of the PLAC test in assessing stroke risk, Iyer said diaDexus did what was basically a new test on a new cohort of patients. Those results were presented last November at the AHA's annual scientific sessions in New Orleans.
Those results suggested that – just as in coronary heart disease – high levels of Lp-PLA2 are believed to trigger a cascade of inflammatory events in atherosclerosis and can independently predict increased risk of stroke, even after accounting for both traditional risk factors, such as blood pressure measurement, and novel cardiovascular risk factors. That conclusion was drawn from analysis by investigators from the ongoing Atherosclerosis Risk in Communities (ARIC) study.
In that study, middle-aged participants with the highest levels of Lp-PLA2 had a statistically significant doubling of risk of suffering an ischemic stroke over a period of about six years compared to those with the lowest levels of the enzyme after taking age, gender and race into consideration.
The company said that even when traditional cardiovascular risk factors such as systolic blood pressure, smoking status and diabetes, and the novel risk marker of systemic inflammation C-reactive protein are accounted for, elevated levels of Lp-PLA2 remained associated with a signficiantly increased stroke risk of almost twofold.
"These ARIC findings illustrate that Lp-PLA2 can be an independent and significant warning – above and beyond standard risk factors – identifying individuals with an increased risk of stroke. Lp-PLA2 may prove to be a useful independent diagnostic measure, and ongoing research is evaluating whether Lp-PLA2 is an important therapeutic target to reduce stroke," said Christie Ballantyne, MD, director of the Center for Cardiovascular Disease Prevention at Baylor College of Medicine and the Methodist DeBakey Heart Center (both Houston) and a lead investigator of ARIC.
The PLAC test for coronary heart disease is currently available through laboratories nationwide, including Quest Diagnostics (Teterboro, New Jersey), Mayo Medical Laboratories (Rochester, Minnesota) and ARUP Laboratories (Salt Lake City).
Iyer told MDD that the PLAC test for coronary heart disease is getting "a reasonable reception" in the marketplace. That test, which Iyer emphasizes is for those with chronic disease for the purpose of assessing risk in the future, is being targeted at primary care physicians.
"Inasmuch as there have been efforts by our lab partners to reach out to the high prescribers and so forth, we've had a pretty good response," he said.
The hurdle for this small company is that it doesn't have its own sales team and that "many people aren't aware," particularly primary care physicians, that the test is approved, he said.
"That's basically our challenge as a small company, and what we're doing is we have now set up a medical science liaison and national sales accounts, and [we've been] rolling that out over the last year," Iyer said. "So, that's basically what we are doing, essentially getting the word out there . . . we really have to depend on our lab partners a lot."
Based on diaDexus' research thus far, Iyer said it has not been able to find a competitive test to the PLAC test for ischemic stroke, although the company is still investigating that. However, he noted that for use in emergency rooms and for acute settings, Biosite (San Diego) is working on a stroke assay panel to determine if a person is currently experiencing a stroke.
Biosite said in late February (MDD, Feb. 23, 2005) that the FDA has accepted the company's Triage Stroke Panel premarket approval application (PMA) for further review. It said the panel is intended for use as an aid in the assessment and diagnosis of cerebral ischemia, or stroke. The company said that the Triage Stroke Panel consists of "multiple biomarkers and uses a proprietary algorithm to calculate a single MultiMarker Index result."
Biosite submitted its PMA for the Triage Stroke Panel in December.