NEW YORK (GenomeWeb) – Proteomic diagnostic firm Prevencio and collaborating researchers this week published a study in the Journal of the American College of Cardiology that indicates the company's protein test for obstructive coronary artery disease could significantly outperform existing tests for the condition.
According to Rhonda Rhyne, Prevencio's president and CEO, the company is now in the process of developing an assay kit for a study it plans to launch next year to generate data for a US Food and Drug Administration submission.
The company also plans to open a $20 million Series C funding round in the second quarter of this year to fund the assay kit development and FDA study, Rhyne said.
In the JACC study, researchers used a training cohort of 649 subjects and a validation cohort of 278 subjects to develop and evaluate the ability of a four-protein panel (midkine, adiponectin, apolipoprotein C-I, and kidney injury molecule-1) combined with patient sex and history of previous percutaneous coronary intervention to identify patients with 70 percent or greater obstruction of at least one major coronary artery.
The test, which Prevencio has named HART CAD, was able to identify patients with coronary artery disease with an area under the curve (AUC) of .87. This compared to an AUC of .52 for conventional stress testing done on the same set of patients.
James Januzzi, a cardiologist at Massachusetts General Hospital and author on the JACC paper, described the work as a "proof-of-concept study" demonstrating that it is possible to identify circulating protein markers "predictive of significant coronary artery disease."
The next steps, he added, would include expanding the studies to additional populations to investigate the test's performance in a range of settings.
"We'd like to know if it can be used, for instance, in the office when a patient is seeing their primary care physician," he said. "We'd like to know if it could be used in the emergency department setting when a patient comes in complaining of chest discomfort. You can imagine the potential application for this type of an approach is quite substantial."
The JACC study was done in samples from the CASABLANCA study cohort, a group of 1,251 patients who underwent coronary and peripheral angiography at Mass General between 2008 and 2011. According to the study authors, these patients were referred for these procedures for reasons including myocardial infarction, unstable angina pectoris, and heart failure, along with nonacute indications like evaluation of stable chest pain and failed stress testing or pre-operative evaluation before heart valve surgery.
"It really covers a broad cross section of different patient types in cardiology," Januzzi said. "However, it's important to caution that they had a reason for being in the [catheterization laboratory]. That inevitably raises the question of whether the population is somewhat more enriched than a general population for the true positive."
Initially, Prevencio will position the test for use as part of the workup for patients that have been referred for a coronary angiogram to evaluate blockage, Rhyne said. The FDA trial the company is planning will look at around 2,000 patients who have received a coronary angiogram, which she noted is the gold standard for obstructive coronary artery disease diagnosis.
However, this procedure is expensive (costing up to $47,000 according to Rhyne) and involves radiation exposure. in addition, according to numbers from Prevencio it is ultimately unnecessary in up to 65 percent of patients who undergo it. The HART CAD could serve as a lower-cost, less-invasive test for identifying patients at high risk for coronary artery disease who should be passed on for CT angiograms.
Stress tests, in which patients typically walk on a treadmill while having their blood pressure and EKG monitored, are used for this purpose, but the JACC data suggests the HART CAD test could significantly outperform this procedure.
Januzzi noted that in the JACC study the panel showed both high negative and positive predictive value, suggesting it could be useful both as a test for ruling patients in for further workup and ruling them out as being at low risk.
"Most biomarkers have good negative predictive value, but their positive predictive value isn't as good," he said. "In this case, actually, we had really well-balanced positive and negative predictive value, which is really kind of unique."
Using a single cutoff, the test had a PPV of 90 percent. In a different scoring model in which patients were broken down into five groups according to their risk levels, the highest risk level (a score of 5) gave a PPV of 93 percent, while the lowest (a score of 1) gave a NPV of 91 percent.
42 percent of the patients in the study's validation set fell into either group 5 or group 1, meaning "you can rule out or rule in nearly half the patients," said Januzzi, who is not employed by Prevencio but has received grants from the company and collaborated with it on studies.
Rhyne said Prevencio is currently in discussions with a number of potential partners about developing the test as a kit for use on their platforms and that it will begin the planned 2,000-patient trial as soon as a kit is ready — most likely the middle of 2018.
The company will fund this effort with a planned $20 million Series C round. That round will roll in $2 million in funds Prevencio raised last year via a convertible notes offering, making for $18 million in new investment, which, Rhyne said, will carry the firm through the FDA submission and clearance process.
At the end of that process, the company will do another raise to support commercialization of the test, she said. She added that another potential outcome at that time is the acquisition of Prevencio by a larger diagnostics company.