NEW YORK – More than a year after getting clearance from the US Food and Drug Administration, infectious disease diagnostic firm Immunexpress has begun commercialization of its near-patient sepsis diagnostic test in the US.
Called SeptiCyte Rapid, the test has been CE-marked and available in Europe since 2020, and the US is the next frontier, said Rollie Carlson, the company's CEO. The qPCR-based assay runs on Biocartis' handheld Idylla platform, and Immunexpress has partnered with the Belgian molecular diagnostics firm to sell the platform along with its sepsis test.
Although it received FDA clearance in 2021, commercialization efforts in the US were delayed because the firm had to scale up its manufacturing in the first quarter of 2022, Carlson said. The company also had difficulty accessing hospitals and customers due to the Omicron surge last year, causing additional delays.
Seattle- and Brisbane, Australia-based Immunexpress began as a biomarker discovery company using microarrays and next-generation sequencing to target genes that were either up-regulated or down-regulated in sepsis, Carlson said. The company developed a laboratory-based test, SeptiCyte Lab, but after feedback from physicians requesting a shorter turnaround time, the company also developed a fully automated, rapid version of the assay.
From a one-milliliter whole blood sample, the test detects two genes, phospholipase A2 group VII platelet activating factor (PLA2G7) and placental-specific 8 (PLAC8), that are expressed in white blood cells when a patient is experiencing the cytokine cascade that indicates sepsis. Specifically, it differentiates how the two genes are expressed during sepsis. During an inflammatory response caused by a pathogen that will lead to sepsis, PLAC8 is overexpressed while PLA2G7 stays stable, while during a general systemic inflammatory response, which has similar symptoms to sepsis but isn't caused by a pathogen, PLAC8 is stable and PLA2G7 is down-regulated, Carlson said.
SeptiCyte Rapid is a rule-in, rule-out test that returns a SeptiScore between 1 and 15 that indicates the probability of sepsis within 60 minutes. If the score is above 7, clinicians can then prioritize the blood cultures to determine the pathogen causing the response and select a treatment. If the patient has a lower score, physicians can look for another cause of the symptoms. The test can also detect sepsis from all three pathogen classes: bacterial, viral, and fungal, Carlson added. By determining whether patients have sepsis, the test is useful in guiding clinician decisions for these patients, he said.
Immunexpress is also building further momentum off data from a recent paper published in Nature Scientific Reports that evaluated the test for use with COVID-19 patients. A study of 146 patients at a hospital in Barcelona found that the test was able to stratify COVID-19 cases according to clinical severity and that the discrimination between cases was better than tests that use other markers, such as C-reactive protein, lactate, creatine, interleukin-6, or d-dimer. The study also found that the test could be used to predict admission to the hospital's intensive care unit.
In addition to the Nature study, the firm is preparing to publish a validation study this year — a preprint was published in MedRxiv in August, which found that the rapid test performance is comparable to the lab-based test's performance, with the rapid test indicating an elevated risk of sepsis in 90 percent of blood culture-confirmed sepsis cases.
Immunexpress sees the assay being used primarily as a test for people sick enough to land in a hospital ICU, with clinicians particularly interested in it as an option for post-operative patients, Carlson said. The hospital setting is the largest opportunity for the test and the company's focus, though in the future, SeptiCyte Rapid could potentially be used in nursing homes.
Carlson said the benefit of the test is that it is used "at the top of the diagnostic triage tree," where time is of the essence, and that it can be applied in conjunction with other tests commonly used to diagnose sepsis, such as those measuring procalcitonin and lactate.
Because SeptiCyte Rapid cannot determine whether the cause of sepsis is bacterial, viral, or fungal, it should not be used to prescribe a therapy. However, Jorge Parada, a professor of public health sciences and infectious disease at Loyola University Chicago and one of the authors of the preprint, said via email that the test can still potentially inform clinicians that antimicrobials may not be warranted, improving antimicrobial stewardship by de-escalating the use of such therapies.
SeptiCyte Rapid, which helps to rule out whether a systemic inflammatory response is due to an infection, provides "very valuable information, because it can reduce use of antimicrobials," he said.
Right now, when a patient has a severe systemic inflammatory response and physicians do not have a lot of information about the cause of the response, "the default is to treat them as infectious, period," he noted. "Not being able to rule out infection means that everyone is treated as having an infection, and everyone gets antimicrobial therapy."
According to the US Centers for Disease Control and Prevention, at least 1.7 million Americans develop sepsis each year, and the number is rising. Determining whether a patient has sepsis and its cause can be a tricky, complicated, and time-consuming process that calls for several testing methods, and often, a diagnosis is based on evaluating a patient's symptoms. To help in the diagnosis, a number of firms are developing or have developed tests aimed at simplifying and accelerating the process, including BioMérieux's BioFire Diagnostics, T2 Biosystems, and Blu Biotech.
Several research groups and companies are also, like Immunexpress, leveraging gene expression technology. Researchers from the University of Oxford and the Wellcome Sanger Institute have developed a sepsis risk stratification method that uses gene expression testing and machine learning, although it has not yet been clinically implemented. Another company, Inflammatix, uses gene expression to measure a patient's immune response and determine whether a patient has a bacterial infection or a viral infection, as well as the severity of a patient's condition.
Other small companies like Nostics and Nanomix are also working on rapid sepsis tests, although Carlson noted that many competitors are detecting the pathogen itself rather than the host response. A German diagnostic firm, Molzym, is developing a platform to detect and identify bacterial and fungal pathogens in patients with sepsis, and Great North Research and Innovation, a UK startup, is working on a test to identify bacteria or fungi in sepsis patients within two hours.
Although the initial indication for the Immunexpress test is in adults, Carlson noted that the company is conducting clinical trials in the US and Australia for extending the test to pediatric patients.
In addition to the European and US markets, Immunexpress is seeking regulatory approval for the test in Australia and is open for partnerships elsewhere, Carlson said. Biocartis has a distribution agreement for the assay in Europe. In the US, Immunexpress is currently marketing the test itself but is also seeking partnerships for distribution, he noted.
As its test has been increasingly adopted in Europe, Carlson said the company has seen other uses for it, including measuring a patient's risk score when they're discharged to predict the chance of readmission.
The firm is also conducting clinical evaluations on a new version of the test, SeptiCyte Rapid Plus, which has gene expression markers to differentiate between a bacterial pathogen and a viral pathogen causing the immune response, in addition to providing the risk score.
Carlson said that the host response technologies it has patented could be applied to other diseases, such as tuberculosis and herpes, and that with additional funding or a partner, the applications could expand.