NEW YORK – With receipt of CE marking last week, Nanomix edged closer to the launch of its first product, a nanosensor-based electrochemical platform that uses three biomarkers in testing for sepsis at the point of care.
The firm's announcement that it had received the CE mark for its SI Assay and eLab instrument represents "the culmination of a number of years of technology and clinical development, and signals a move into a new phase for the company as a commercial operation with R&D support," its President and CEO David Ludvigson said in an interview.
Nanomix is engaging with global distributors and preparing a regulatory submission for US marketing clearance to the US Food and Drug Administration in the first quarter of next year. For that, the firm is leveraging the test validation data it used to obtain CE marking, which was gathered during US-based multicenter clinical trials.
The Emeryville, California-based firm's new test simultaneously detects and quantifies lactate, procalcitonin, and C-reactive protein from human plasma specimens within 11 minutes in point-of-care settings, such as hospital emergency rooms and facilities with skilled healthcare workers outside hospitals. Ludvigson said that during analytical validation testing, in preparation for CE marking, the system demonstrated laboratory-quality testing capabilities.
The fully automated Nanomix eLab System consists of a handheld reader and an integrated, self-contained assay cartridge with a nanosensor. The system's three biomarkers are already used along with clinical inputs, such as symptoms and patient history, by physicians looking to decide whether someone may have sepsis.
The eLab system uses a microfluidic cartridge and solid-state electrochemical detection to run enzymatic assays and immunoassays that identify lactate enzymes, a marker of tissue profusion; c-reactive protein, a marker of inflammation; and procalcitonin, a marker of bacterial infection.
Notably, the impending launch of this product in 2020 would represent the first time that the three markers will be made available simultaneously on a single platform for point-of-care testing, said Tom Richards, a senior advisor to Nanomix who specializes in sepsis diagnosis. The platform provides the benefit of eliminating the sending of samples to laboratories and should, therefore, reduce significantly the amount of time physicians must wait to get test results that inform their decision-making associated with therapy, said Richards, who was once an emergency room physician and is a former interim CEO of Singapore-based One Biomed.
Lactate is available for measurement by point-of-care instruments, such as Abbott's iStat. However, Abbott's instrument is one of three systems that investigators have used to compare the performance of the Nanomix instrument during clinical trials. Nanomix has also compared the performance of its test with current tests for C-reactive protein using the Abaxis Piccolo Xpress and procalcitonin using the Biomérieux Mini Vidas.
"The three assays that they have chosen to put on the panel are by far the most common biomarkers used in the evaluation of serious bacterial infections and sepsis," Richards said.
The platform is suitable, he said, for use in hospital emergency rooms and for settings outside hospitals where infections are prevalent, including post-surgical and elderly care facilities. Nanomix is engaged with clinical partners to develop a future version of the platform that operates using whole blood, which would target use by emergency medical service first responders.
Receipt of the recent regulatory clearance allows Nanomix to start discussions with additional distribution partners throughout the territories that recognize the CE mark, Ludvigson said.
To enable distribution, the firm has inked agreements with two partners. One of its investors, RedPharm Biotechnology, will distribute the firm's products in South East Asia. Kalamazoo, Michigan-based Stryker will distribute the products globally with a focus on targeting pre-hospital and emergency department placements.
The firm is currently developing the whole blood version of the product with clinical partners and expects to complete development in 2020, enabling use of the platform by emergency medical system first responders.
Nanomix did not disclose the price of its instrument. Ludvigson pointed out that the three tests that run on the system are covered by reimbursement codes. Based on reimbursement rates, "you are looking at a maximum of $50 to $60 for an 11-minute test to determine the infectious state of a patient," he said.
The addressable market is sizable, "at around 15 million tests per year" in developed countries for front-end screening of people presenting with serious infections, Ludvigson said.
Given the complexity associated with sepsis diagnostic testing, several firms are developing platforms that include several biomarkers. Just as many different types of diagnostic tests are in use to help clinicians diagnose sepsis, many biomarkers are also needed to help clinicians diagnose a disease such as sepsis, which consists of such diagnostic complexity, Richards said.
Mologic is among the companies developing a multimarker diagnostic test for sepsis. Its lateral flow point-of-care technology includes six undisclosed host-response biomarkers.
Stanford University spinout Inflammatix and Duke University spinout Predigen Diagnostics are separately developing sepsis tests that leverage gene expression associated with the immune system's response to infection.
Ephraim Tsalik, a cofounder of Predigen and associate professor of medicine at Duke, said in an interview that when you break the definition of sepsis into its multiple components, there are uses for multiple types of diagnostic tests. The first, which includes tests produced by Accelerate Diagnostics, T2 Biosystems, Biomérieux, and others, focuses on the infection component. "The assumption is that if you find the pathogen, then you’ve identified the source of the sepsis," Tsalik said. "There are some caveats. First, just because a patient has an identified pathogen, it doesn’t mean they have sepsis. The majority of patients with infection do not have sepsis. Moreover, just because you have sepsis, it doesn’t mean a pathogen will be found."
Another component of the sepsis diagnosis is the presence of organ dysfunction. However, the most challenging part is identifying the dysregulated host response, Tsalik said. "This is what lactate aims to do – it can reveal tissue hypoperfusion even when the blood pressure is normal. As such, it is used as a screening tool to identify possible sepsis and is part of the sepsis guidelines."
CRP is a non-specific biomarker of inflammation, although very high levels correlate with bacterial infections and with sepsis. Procalcitonin is "an inflammatory marker that correlates with the presence of sepsis, but is too unreliable to guide any initial management," he noted.
Nonetheless, Tsalik said, the Nanomix product is interesting. "Specifically, the ability to measure all three biomarkers at the point of care in a very fast format is definitely innovative. …The next step has to actually put this test into clinical environments to see how it performs and most importantly decide whether it makes a difference in clinical care. … The company, in my mind, needs to demonstrate in the literature how the test worked in users’ hands and most importantly what clinical utility it offers."
The host immune response to infections is so heterogeneous that multimarker tests "will be the only way to make real gains in clinical practice," Tim Sweeney, cofounder and CEO of Inflammatix, said in an interview. "We and others are working on Multianalyte Assays with Algorithmic Analysis tests that both measure multiple markers and then integrate the results with machine-learning algorithms to better detect infections and predict sepsis. This can give rise to better accuracy than any individual biomarker alone."
With the Nanomix product, "assuming that the performance is similar to existing tests, it sounds like the major innovations are the speed of the results and the fact that these three tests are bundled," Sweeney said. "In this case, a bundle of biomarkers without an integrating algorithm is asking the physician to be the algorithm — to integrate lactate, PCT, and CRP."