Diagnostics company Sphingotec GmbH is looking to break into the U.S. market with a pair of biomarker assays that could help determine the best treatment for critically ill patients at risk for septic shock.
The two assays, which are run on the company’s point-of-care Nexus IB10 immunoassay platform, measure bioactive adrenomedullin (bio-ADM), a hormone that maintains endothelial function; and dipeptidyl peptidase 3 (DPP3), an enzyme that inactivates angiotensin II when released into the blood. Both molecules have been shown to be associated with adverse outcomes in sepsis, leading to septic shock and greater risk of death.
The assays can help clinicians better determine if patients are likely to have a severe course of disease and if they are likely to respond to standard of care treatments, such as vasopressors, or if those medications will worsen their outcomes. In the future, it could also help with the development and testing of novel targeted treatments, according to Sphingotec CEO Andreas Bergmann.
“This was a blind spot in the eyes of clinicians for many years. They had seen many patients die due to loss of heart function, but they didn’t know why,” Bergmann told BioWorld.
The Nexus analyzer and the two sepsis biomarkers achieved CE marking in Europe in 2020 and are currently being sold there.
Hennigsdorf, Germany-based Sphingotec is planning a submission to the U.S. FDA for registration of the analyzer and the two biomarkers sometime in 2021. They plan to follow that registration with the launch of a prospective, observational study that would form the basis for a de novo clearance submission by 2023, according to Bergmann.
Two distinct pathways
A series of studies over the last two years have begun to sketch a clearer picture of how sepsis and septic shock occur in critically ill patients. In December 2020, researchers at Radboud University in The Netherlands published a review in the Journal of Internal Medicine describing “two unique and distinct pathways of clinical significance involved in the development of septic shock.”
One process involves ADM, a hormone involved in regulating vascular tone and endothelial barrier function. The increased release of ADM is thought to be related to capillary leakage and the loss of tissue resistance, which is one pathway to septic shock. The other process involves DPP3, a cytosolic enzyme involved in degrading signal molecules that regulate vascular tone, notably angiotensin II. The depletion of angiotensin II leads to cardiac depression, otherwise known as refractory shock.
In another recently published paper, researchers found that there was a strong association between high levels of circulating DPP3 in plasma at the time of admission to the ICU and short- and mid-term clinical outcomes. Conversely, normalization of circulating DPP3 levels early in a patient’s ICU stay was linked with lower mortality. These findings were published in February 2021 in Critical Care.
The Sphingotec biomarkers are designed to be used either in the laboratory or at the point of care to quantify the level of either the ADM hormone or the DPP3 enzyme in a patient’s blood. If the levels are elevated, that indicates that a patient may be at risk for septic shock, according to the company.
The Nexus IB10 system analyzes whole blood samples that are positioned on a compact disc with a pipette and inserted into the portable analyzer. Sphingotec estimates that the preparation of the sample takes about three minutes, while the processing of sample is completed in about 20 minutes. The fully automated analyzer produces quantitative results that can be printed or connected to a Laboratory Information Management System.
The Sphingotec technology, specifically the bio-ADM biomarker, could also have clinical utility in the management of hospitalized patients with COVID-19, Bergmann said. Recent studies have shown that inflammation-induced damage of vascular endothelial cells occurs often with COVID-19, suggesting that utilizing a biomarker of endothelial dysfunction could help identify patients who need ventilation or are at risk for kidney dysfunction, Bergmann said.
“The loss of vascular integrity is causing the need for ventilation,” he said. “Fluids are entering into the lungs due to leaking blood vessels and then lung function goes down and bio-ADM goes up.”
There is also emerging research showing that DPP3 may be part of the COVID-19 process as well, he said.
Bergmann said the company plans to submit information to the FDA seeking emergency use authorization of the Nexus IB10 immunoassay platform in conjunction with the bio-ADM biomarker assay for hospitalized COVID-19 patients.