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Studies Highlight Potential Expanded Use for Singulex Troponin Assay


NEW YORK (360Dx) – A series of recent publications have highlighted the potential of high-sensitivity troponin testing using Singulex's single-molecule counting technology to aid in the clinical care of heart patients not only in the acute setting, but also for risk assessment of more stable patients.

In one study called CASABLANCA, published earlier this month in the Journal of the American Heart Association, researchers studied patients referred for diagnostic coronary angiography, hoping to see whether troponin levels would correlate with the presence of coronary artery disease and predict incident cardiovascular events and mortality.

The group studied samples from 991 patients obtained at the time of angiography, and found that patients with higher troponin levels had higher prevalence of angiographic CAD and were more likely to suffer a later heart attack, to die due to cardiovascular disease, or to die for any reason.

Another study in the March issue of the Journal of the American College of Cardiology Imaging, found that measurement of cardiac troponin in stable patients with chest pain using Singulex's assay could independently predict moderate and severe coronary disease.

This trial, called PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) measured troponin in 1,844 outpatients with stable chest pain who were randomized to coronary computed tomography angiography (CTA).

After adjusting for demographic and clinical characteristics, investigators reported that troponin concentrations as measured by the Singulex platform, were significantly associated with obstructive CAD and CAD.

A third study, which appeared in February in Circulation: Cardiovascular Quality and Outcomes similarly concluded that the Singulex test could independently predict moderate and severe coronary artery disease.

Using it's single-molecule counting Clarity instrument, Singulex claims it can achieve 1,000 times more sensitivity than competing technologies that are considered capable of high-sensitivity troponin detection. The firm says that its test is the first to measure cardiac troponin down to femtogram per milliliter levels.

James Januzzi, a lead author of both the PROMISE and CASABLANCA analyses, said in an email this week that the two studies support a role for high-sensitivity troponin testing not only for diagnosing or ruling out heart attack, but to help clinicians assess patients for CAD.

"We found in both trials that concentrations of the Singulex hsTnI predict presence and severity of obstructive CAD. Furthermore, in CASABLANCA, such concentrations were prognostic for future adverse events," he wrote.

"We believe this suggests a potential role for hsTn testing in more stable patients, compared to the present model, where they are measured in those patients suspected of having an acute" myocardial infarction, he added.

High-sensitivity troponin assays have been available in Europe for some time, but none were approved by the US Food and Drug Administration until last year when the agency cleared Roche's Elecsys Troponin T Gen 5 STAT.

The FDA cleared Roche's assay to aid in diagnosing a heart attack in patients who present with clinical symptoms. This is the same indication that Singulex is pursuing with its 510(k) for the Clarity system in the US, at least initially, recognizing that it needs approval of its system in an established indication first, before it can begin the process of expanding.

In Europe, high-sensitivity troponin is used in other ways, as well — for example, to rule out heart attack or cardiac ischemia, in order to guide patients away from unnecessary follow-up testing. Singulex has gotten a CE mark for the use of its platform in ruling out ischemia, and has said it ultimately hopes to include that use in the US, as well.

But broader use of troponin in assessing cardiovascular risk in a non-acute setting is a relatively novel proposition for US cardiologists.

According to Januzzi, much more data will be needed to confirm the results he and his colleagues saw in CASABLANCA, and more importantly, to really nail down how to apply the results of this testing into the clinical work flow for patients with a more stable CAD presentation. 

"It is possible that [high-sensitivity troponin] could play as important — if not more important — a role in patients with more stable presentations, possibly identifying those patients [who would benefit] from precision application of therapies," he said. "This may be treatments to more aggressively lower lipids (such as PCSK9 inhibitors), direct oral anticoagulants (such as rivaroxaban), or therapies targeting metabolic disorders (such as the SGLT2 inhibitors)."

"We have a sense each of these therapies are of benefit — particularly for higher-risk patients — but there is a large amount of clinician inertia present regarding who should, or should not, receive these newer and sometimes more expensive therapies."

Januzzi reiterated that Singulex is not the only entity applying a high-sensitivity technology platform to troponin testing, and is most likely not alone in collecting evidence to support an expanded use of this testing beyond the acute setting.

"Most of the current high-sensitivity assays are aiming to have this type of application," he wrote. "More and more refined assays — including modifications of those currently commercially available — are coming [but] whether their results will compare to those we found … remains speculative."

Technologies that assess multiple protein biomarkers are also being advanced rapidly, and Januzzi said that it's likely that in the near future, multimarker algorithmic and machine learning strategies may usurp the use of individual biomarkers like troponin.

Januzzi has also worked closely with proteomic diagnostics firm Prevencio, which has been developing its own CAD test.

"It’s not hyperbole to suggest the approach taken by Prevencio is the future of biomarker-supported evaluation and management of patients with cardiovascular disease," he wrote.

"In our studies based in the MGH Heart Center … the multimarker, machine learning strategy is more powerful than the single biomarker approach for every application we’ve examined [including] to predict presence of underlying coronary artery disease," he added.

Singulex President and CEO Guido Baechler said that the company will continue to advance its troponin applications, but is also in the process of shifting its focus to the infectious disease arena, developing a test for Clostridium difficile, where it believes its technology could offer critical improvements in sensitivity and specificity over currently used platforms.