Following completion of a large prospective validation study, BG Medicine has filed for 510(k) clearance from the US Food and Drug Administration for its prognostic test for near-term cardiovascular events.
The firm developed the test, called AMIPredict, with the hope of improving upon standard cardiac risk-assessment methods, such as the widely used Framingham risk score. AMIPredict is intended to help assess a patient's likelihood of suffering a sudden heart attack or stroke, according to Pieter Muntendam, formerly BG Medicine's president and CEO, now executive vice president and chief medical officer.
If approved, the test would be the company's second cardiovascular in vitro diagnostic, following its galectin-3 ELISA test. The latter test is marketed by Laboratory Corporation of America and was cleared by FDA in November 2010 as an aid in predicting the prognosis of patients diagnosed with chronic heart failure.
BG Medicine is basing its FDA submission for AMIPredict, which runs on Abbott's Architect platform, on a recently completed validation study using data from the company's 6,600-patient trial, BioImage.
Muntendam told PGx Reporter that while the assay isn’t intended to be a replacement for other cardiovascular risk assessment measures, the company believes it could help identify high-risk patients who would otherwise be missed by current methods.
"While [cardiac events] are such an enormous problem, there really hasn't been a lot of effort around improving risk identification," Muntendam said.
"The key problem" is that risk-factor-based assessments using criteria like smoking or high blood pressure or diabetes "poorly correlate with actual risk," he said. This suggests that a certain number of patients deemed low risk according to biological risk factors may actually be at a high risk of suffering an acute event.
A test that could pinpoint these high-risk patients could also identify patients who could benefit from preventive therapy — an idea that has spurred the interest of drug developers. Muntendam said the company has received financial support from several pharmaceutical companies, including Merck, Abbott, and AstraZeneca, through a project it has dubbed the High-Risk Plaque Initiative.
"80 percent of [these] events actually occur in people who are considered low-to-medium risk [according to risk-factor-based assessment.] So the key question we [have tried] to address is, 'Can you pick out the 'low-risk' patients who are in fact walking around with an inflamed vascular tree with plaques at risk for rupture?'" Muntendam posited.
AMIPredict measures seven protein biomarkers in patients' blood and calculates a risk score for near-term acute cardiovascular events. The markers include proteins commonly known to be associated with cardiovascular adverse events, as well as some novel markers that Muntendam implied are integral to the test's accuracy.
"I don't think you'd find a single individual who could correctly name all the key [markers in the test]," he said. "A number [of markers in the panel] are a surprise, and that's the only way to really get a panel that carries a significant signal."
BG Medicine has been relatively cautious in its approach to commercializing AMIPredict. The company is planning further validation studies, but does not plan to market the assay ahead of its IVD submission.
"We believe a test that makes this kind of claim really should be subject to FDA approval," Muntendam said, adding that while a number of companies have laboratory-developed tests in the space, he believes the days of companies "circumventing" the FDA are numbered.
"Payors and patients expect that if a test is good, there shouldn't be anything in the way of getting FDA approval," he argued.
BG Medicine collaborated with Humana to conduct the BioImage trial, which is the backbone of its 510(k) filing for the test. The trial enrolled about 7,000 members from the insurer's Medicare group, a cohort that mirrors the intended population for the test.
In the study, the company investigated whether AMIPredict was as good as or better than standard risk assessment methods, such as coronary calcium scanning, which uses CT scanning to image calcium deposits in the coronary arteries.
Coronary calcium scanning is "fairly well accepted in terms of performance," Muntendam noted, adding that the method has "a number of key drawbacks to widespread adoption," including issues of radiation exposure as well as scalability. According to Muntendam, validation data from the BioImage trial showed that AMIPredict provides risk information on par with coronary calcium scanning.
Muntendam did not elaborate on the assay's specific accuracy, noting that the company is not disclosing comprehensive results until it publishes the study in a scientific journal.
In order for AMIPredict to be successfully adopted into medical care in the heart disease market, the test will likely have to show it adds value beyond standard clinical measures of risk. For example, there has been significant debate over physician resistance to using CYP2C19 genotyping to prognose disease risk and predict best responders to the antiplatelet drug Plavix.
In late 2010, the Centers for Disease Control and Prevention's Evaluation of Genomic Applications in Practice and Prevention Working Group reviewed a number of prognostic cardiovascular disease-tests and reported that the "magnitude of net health benefit" from the use of eight tests available at the time was "negligible" (PGx Reporter 11/10/2010). The working group highlighted the need for large studies that seek to reduce bias and compare the usefulness of genomic markers to traditional risk factors, such as those used in the Framingham risk score.
Muntendam stressed that AMIPredict is not intended to replace broad risk-assessment tools like the Framingham risk score, which combines a number of factors including cigarette smoking, blood pressure, and age and is used to establish a patient's 10-year cardiovascular risk. But, he said, adding the AMIPredict test to such measures could help reveal additional at-risk individuals.
For this reason, BG Medicine has enjoyed support from several industry partners through the High-Risk Plaque Initiative, a joint research initiative, sponsored by several pharmaceutical companies, that aims to discover methods for early identification of individuals at risk for heart attack and stroke.
"The pharmaceutical industry concluded that this is an important unmet medical need, and also creates a new therapeutic opportunity," said Muntendam. "[They] wanted to support our discovery efforts because of the potential to have a group of high-risk patients that can be treated.
"We all know a healthy 62 year old who drops dead from a massive heart attack, which is really our target group," he said.
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