December 1, 2016 (Vol. 36, No. 21)
To Detect Sepsis Quickly, Says Immunexpress, Track the Host Response, Not the Pathogens
When Immunexpress tackled the challenge of diagnosing sepsis quickly and accurately, its first step was to eschew the traditional pathogen-based method in favor of using the patient’s immune system to determine infection. Now, rather than attempting to identify pathogens in blood samples, Immunexpress interrogates just a few genes to identify the subtle changes in expression that can indicate sepsis even in its very early stages. Results are available in under 3 hours instead of the average 72 hours needed for pathogen culture, identification, and antibiotic-sensitivity determination.
Early Detection Possible
“The SeptiCyte™ technology is designed to detect infection in suspected sepsis patients at any stage in the disease cascade, from early- to late-stage,” says Roslyn Brandon, D.V.M., Ph.D., Immunexpress’ president and CEO.
This molecular diagnostic assay is meant to complement, rather than replace, current pathogen-based diagnostic approaches, she explains: “SeptiCyte would be the first port-of-call to identify the condition and the pathogen type more quickly, and to be used in conjunction with other clinical and laboratory assessments.”
Sepsis diagnosis begins with a blood draw. “SeptiCyte requires only a couple of milliliters of blood, which is easy and particularly helpful with children,” Dr. Brandon notes. Then, the sample is run on a reverse transcription quantitative polymerase chain reaction (RT-qPCR) instrument to measure slight changes in expression of biomarkers involving four key genes. An algorithm converts that complex data into a score indicating the probability of sepsis.
The initial SeptiCyte products are designed for hospital core laboratories, but the assay is instrument-agnostic, so it is transportable to a variety of diagnostic instruments. Dr. Brandon anticipates receiving FDA clearance in the first half of 2017.
SeptiCyte also is being developed for use with point-of-care instruments for faster results in other healthcare environments. Eventually, Immunexpress plans to create a highly automated version for intensive care units and emergency rooms that may deliver results within one hour.
For such a speedy response time to become a reality, however, requires further development and automation of the instruments that run the tests. “The industry today still lacks the technology to turn around gene expression results in one hour,” Dr. Brandon advises, “but it’s getting close.”
Positive Clinical Trials
“We have just completed a pivotal trial in around 450 adult patients at eight clinical sites,” Dr. Brandon reports. This trial, called VENUS, is a prospective observational study to validate SeptiCyte to differentiate between sepsis and noninfectious systemic inflammation.
Immunexpress also just published results showing that SeptiCyte accurately distinguishes between sepsis and noninfectious systemic inflammation in critically ill children. The study, which was conducted at Seattle Children’s Hospital, showed near 100% accuracy regardless of the severity of the host response in children with organ dysfunction.
Additional trials designed to measure both clinical and economic outcomes are among the next milestones. The economic simulations that have been included in each trial are considered promising.
Challenge of Sepsis
Immunexpress is completely focused on diagnostics for better sepsis management, but Dr. Brandon cautions that sepsis is poorly understood. “Many questions remain around sepsis and how to best treat sepsis patients,” she explains. “Our technology is based on the immune system, so our know-how could be applied to other areas. As our product pipeline develops, as many as 16 genes may be interrogated to answer other clinical questions around sepsis.
“Sepsis is a challenging disease. It kills quickly, and current diagnostics are too slow and unreliable. There is no gold standard for diagnosing sepsis. Currently, most of the near-patient point-of-care technologies for infectious disease are designed to detect pathogen. Those assays provide ‘yes’ or ‘no’ answers.”
Additionally, as Dr. Brandon observes, the pathogen needs to be in a blood sample in sufficient quantity to be found. Detection may depend upon the volume of blood, the pathogen load, and dosage of antibiotics. The volume of blood is particularly challenging in neonates and children. “Sepsis pathogen may not be discovered even in very sick patients with severe sepsis who have been treated with antibiotics,” Dr. Brandon emphasizes. “Consequently, there is huge unmet clinical need.”
Molecular diagnostics have become possible only relatively recently, once gene expression technology evolved from the research stage to commercialization. “The necessary instruments for fast, fully automated tests have emerged only in the past few years,” Dr. Brandon points out.
Initially, genomics was focused on cancer, where the need for very fast results is lower, rather than inflammation and infectious disease. One of the reasons, she explains, is that “because cancer is a chronic disease, oncologists don’t need an answer in a couple of hours. In contrast, the ICU and ER physicians who are most likely to see sepsis need results much more quickly because the risk of death increases 7.6% for every hour without treatment.”
For sepsis diagnostics, overcoming long wait times has been a critical hurdle. Immunexpress is overcoming that hurdle, delivering results in hours rather than days.
To advance commercialization, Immunexpress is interested in collaborative ventures and currently is raising Series C funding. The privately owned company is headquartered in Seattle and has offices in Brisbane, Australia.