NEW YORK — SphingoTec's recent launch of a CE-marked test foreshadows a strategic move that involves taking novel biomarkers previously available as manual microtiter-based assays and marketing them on a fully automated, microfluidic immunoassay platform suitable for use at the point of care.
The Hennigsdorf, Germany-based firm last week introduced an assay to quantify blood plasma levels of dipeptidyl peptidase 3, or DPP3, a biomarker that can predict outcomes in patients with cardiogenic shock when they are admitted to hospital intensive care units.
Sphingotest DPP3 is the first of three tests involving novel biomarkers for acute care that the firm anticipates releasing soon on the IB10 point-of-care immunoassay platform that it acquired last October along with the platform's developer, San Diego-based Nexus Dx.
SphingoTec CEO and Founder Andreas Bergmann said in an interview that next month, his firm expects to launch a second biomarker on the platform, adrenomedullin (bio-ADM), a CE-marked test for vascular integrity that measures the peptide hormone bioactive adrenomedullin. Clinicians can use the assay to manage patients with congestive heart failure and monitor whether the patients have residual congestion requiring additional diuretics or whether diuretic treatment can be ended.
Next in the product pipeline, in 2020, SphingoTec anticipates using the POC platform to launch proenkephalin, or penKid, a biomarker of kidney function. The firm's CE-marked proenkephalin assay provides immediate information on how the kidney is functioning and helps clinicians with treatment decisions, Bergmann said.
Both bio-ADM and penKid had previously been available as microtiter assays leveraged by clinicians doing research, and less frequently by clinicians doing diagnostic testing. Moving the biomarkers to the IB10 point-of-care platform represents an important step in the firm's business strategy, Bergmann said.
In treating their patients for acute conditions, clinicians will be able to use the point-of-care platform to combine the three biomarkers and select from among others already available on the system — including procalcitonin, NT-proBNP, troponin I, and D-Dimer. A system that enables use of these markers in a combined fashion can be used to assess patients in intensive care units and emergency rooms, who present with septic shock and cardiogenic shock, or are undergoing potentially fatal surgeries, among other conditions.
"SphingoTec will continue to sell the existing biomarker tests but now we are adding that proprietary content to the platform via the novel biomarkers and combining all of the biomarkers in an intelligent way for specific indications," Bergmann said.
The portable microfluidic platform acquired with Nexus Dx resembles a compact disc player, he noted. Whole blood inserted into the platform fills separate chambers without the need for pipetting. The test doesn't require calibration or sample preparation because plasma separation occurs in a reagent disc. Following an incubation period of 20 minutes, the platform provides a quantitative test result that can be printed, loaded to a laboratory information system, or sent to a clinician via an email or SMS mobile message.
When the firm acquired Nexus Dx, more than 1,000 intensive care units, emergency departments, small hospitals, and large practices in Europe and the Middle East were already using the platform for more than 100,000 tests per year.
To support rolling out of its biomarkers on the IB10 point-of-care platform, Sphingotec closed a €20 million ($23 million) growth equity financing round in 2018.
For lab technicians, the platform is notably different from the microtiter-based testing format the firm has been using, Bergmann said.
SphingoTec had introduced the bio-ADM and penKid biomarkers as microtiter-based assays primarily for research use about two years ago. Investigators have validated the biomarkers in more than 50,000 patients and in numerous clinical studies, Bergmann said, mostly in Europe but also in Asia and the US. Though the microtiter-based biomarker tests have also been placed in around 40 clinics in Europe for routine diagnostic testing in ICUs and emergency departments, the manual workflow that it entails is holding back adoption, Bergmann said.
The firm decided to implement the biomarkers on the point-of-care platform as part of a strategy that also involves outlicensing the use of the biomarkers to diagnostic companies for placement on their laboratory-based analyzers.
Bergman said that he believes adoption of the point-of-care platform and its assays help prove the relevance of the biomarkers for use on large instruments by licensing partners.
In 2017, Ortho Clinical Diagnostics became the first company to license the SphingoTec bio-ADM immunoassay for use on a core laboratory platform, the automated Vitros immunodiagnostics and integrated systems.
Fernando Chaves, the global head of medical, clinical, and scientific affairs at Ortho, said in an interview that the firm is validating the test on the Vitros platform and preparing for clinical trials in advance of a submission to the US Food and Drug Administration.
Overall, the IB10 platform is a step forward for acute care because it "enables a very simple deployment of the novel biomarkers in a near-patient setting or in a lab, and will allow testing with those biomarkers along with the other critical-care markers in a near-patient setting," Bergmann said. The platform can combine up to five protein biomarker tests using a single patient sample. A clinician could integrate testing for procalcitonin, a biomarker used to diagnose sepsis that is already on the platform, with bio-ADM and penKid in the evaluation of a patient suspected of undergoing septic shock, he further noted.
Use of the novel biomarkers on the point-of-care platform helps differentiate SphingoTec from competitors, including Abbott whose iStat platform is used extensively by clinicians at the point of care and Siemens Healthineers' Epoc point-of-care platform, which has also seen significant adoption, Bergmann said.
SphingoTec's recent launch of the DPP3 assay coincides with the presentation of clinical data that revealed that the effects of pathological concentrations of DPP3 were immediately reversed in preclinical disease models upon injection of Procizumab, an anti-DPP3-antibody in preclinical development by 4TEEN4 Pharmaceuticals. Alexandre Mebazaa, a researcher of acute and chronic heart failure at Hôpital Lariboisière in Paris, presented results from published clinical studies associated with DPP3 at the ESC (European Society of Cardiology) Congress 2019 in Paris last week.
Mebazaa and his colleagues developed the DPP3 biomarker with 4TEEN4 and SphingoTec has licensed the global rights to distribute DPP3 on Nexus IB10 from 4TEEN4.
Mebazaa said in an interview that his group has shown in the clinical studies that "DPP3 is highly present in the most severe form of acute heart failure, cardiogenic shock, [and] likely participates in the depression of cardiac contraction in those patients."
More importantly, he said, antibodies against DPP3 restored cardiac function in mice with heart failure, a finding that needs to be confirmed in humans.
Mebazaa said that his group has also validated bio-ADM in a large cohort of intensive care patients and "saw that high bio-ADM in the plasma at admission in the intensive care unit and more importantly before discharge was associated with the highest mortality in the following year."
He added that he and his team has used penKid measurements in several cohorts, mainly to measure the plasma of heart failure patients in intensive care. Those initiatives "consistently showed that penKid could alert on worsening renal function before the classical measures, including creatinine," Mebasaa said.
Serum creatinine levels are frequently used to measure kidney function, but the biomarker appears late as an indication of worsening renal functioning, while the penKid test can be used to monitor that process in real time, SphingoTec said.