With positive data from two validation studies in hand, diagnostics firm Pronota is prepping its acute heart failure protein biomarker CD146 for a 2014 launch.
The company announced last week that two independent validation studies comprising more than 500 patients demonstrated the marker significantly improved diagnosis of acute heart failure in patients presenting with shortness of breath.
According to Pronota CEO Katleen Verleysen, the company is now in the process of putting together prospective clinical trials for CD146 in Europe and the US with the aim of obtaining an EU CE mark next year and US Food and Drug Administration 510(k) clearance in 2015.
In the two validation studies, CD146 showed equivalent diagnostic performance to the widely used acute heart failure marker b-type natriuretic peptide, Verleysen said. However, she told ProteoMonitor, because the two markers are based on different biological mechanisms, Pronota plans to market it for use in concert with BNP. When added to BNP, CD146 improved that marker's diagnostic accuracy by 15 percent, she said.
BNP is associated with damage to heart tissue itself. CD146, on the other hand, is a marker of fluid in the lungs, a common symptom of heart failure. This, Verleysen said, makes it well-suited for sorting out a common problem in heart failure diagnosis — evaluating patients suffering from shortness of breath.
"When patients come in [with shortness of breath], it's extremely challenging to make the distinction [between] shortness of breath due to acute heart failure or due to something else, like pneumonia or another sort of lung infection," she said. Because CD146 is elevated in acute heart failure patients compared to sufferers of other lung conditions, Pronota believes it could prove useful in identifying these cases.
The company discovered and performed initial validation of the marker on its mass spec-based discovery and validation platforms, named MASStermind and MASSterclass, respectively. The former runs on an Applied Biosystems 4800 MALDI TOF/TOF mass spec system, while the latter uses selected-reaction monitoring mass spec on a Thermo Scientific Vantage triple quadrupole machine.
Pronota then converted the marker to a research-use-only ELISA format, which it made available to its collaborator Alexandre Mebazza, a researcher at the French National Institute of Health and Medical Research and leader of the two validation studies the company announced last week.
It is now in the process of converting the RUO assay into a clinical assay for use in its planned EU and US clinical validation trials.
As a single-marker, immunoassay-based test, it should be portable to wide variety of platforms, Verleysen said, adding that Pronota was in discussion with a number of diagnostics companies about licensing.
She suggested that the test might be particularly well-suited to point-of-care devices given that rapid turnaround would be necessary.
"The test results need to be available within an hour," she said. "So it doesn't necessarily have to be point-of-care, but it will need to be quite near the patient ... in the clinical lab of a hospital, for instance."
At around $25 per test, use of CD146 for diagnosis of acute heart failure patients with shortness of breath represents a global market opportunity of around $600 million annually, Verleysen said.
Pronota is also looking into using the marker for home monitoring of chronic heart failure patients at risk of suffering acute decompensated heart failure. Current practice relies on patient weight measurements to track fluid buildup in the lungs — a potential warning sign. This approach, though, is complicated by unrelated fluctuations in patient weight, Verleysen said, making a more objective measure like CD146 desirable. The company has not yet conducted clinical studies examining the effectiveness of the marker for this specific purpose, she said, but believes it could prove useful based on its underlying biology.
Verleysen added that the company also sees a place for the marker in monitoring heart failure patients for reduction in lung fluid volume before their release from the hospital. Such an application, she said, has become particularly interesting from a business perspective in light of the Centers for Medicare and Medicaid Services' recent implementation of guidelines with penalties aimed at reducing hospital readmissions.
As part of the Affordable Care Act, CMS has begun fining hospitals it identifies as having too many patient readmissions, with the maximum penalty being a 1 percent reduction in Medicare payments for every patient over the next year. This has created an incentive for hospitals to lower their patient readmission rates, and has presented an opportunity, Verleysen noted, for a marker like CD146 that could help better identify when a heart failure patient is, in fact, ready to go home.
In this regard the company's strategy mirrors that of diagnostics firm BG Medicine, which is also targeting the hospital readmission market with its heart failure protein marker galectin-3. BG announced its plans to target this space last fall and has since published two studies suggesting that galectin-3 testing can help reduce unwanted readmissions (PM 3/8/2013).
Though also focused on acute heart failure, BG's galectin-3 test isn't a likely competitor for CD146, Verleysen said, noting that the former is used primarily for predicting heart failure risk as opposed to diagnosing the condition.
The company could, however, face competition in the home monitoring realm from Alere, which is currently exploring the use of BNP in this setting. This week a team led by Alere researchers published a study in the Journal of the American College of Cardiology indicating, the authors wrote, that "BNP testing is feasible and that trials using home monitoring for guiding therapy are justifiable in high-risk patients."
"Daily weight monitoring is complementary to BNP, but BNP changes correspond to larger changes in risk, both upward and downward," they added. In total, the JACC study examined 163 patients, tracking their weight and BNP levels for 60 days after hospital discharge.
In addition to CD146, Pronota is developing as cardiac biomarkers the protein quiescin Q6 (QSOX1), which it also intends as a complement to BNP in heart failure diagnosis, and latent transforming growth factor binding protein 2 (LTBP2), which it is exploring as a prognostic marker for dyspnea patients.
It also has biomarker programs for conditions including pre-eclampsia, ovarian cancer, and sepsis. Beyond CD146, the most advanced of these is its pre-eclampsia program, for which the company is currently preparing a 10-site, 5,000-patient clinical trial that it aims to complete over the next two years (PM 11/9/2012).