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Cytovale Preparing to Launch Sepsis Risk-Scoring Test


NEW YORK – Cytovale said it is weeks away from launching its 10-minute sepsis test that it says can help physicians identify which patients are at the highest risk of sepsis, which treatments are warranted, and when to look for alternate causes for a patient's symptoms.

The San Francisco-based firm nabbed U.S. Food and Drug Administration 510(k) clearance in December 2022 for its IntelliSep prognostic blood-based test intended to help emergency departments stratify patients by sepsis risk by using the results along with a clinician's judgment. The test uses high-speed imaging and machine learning to assess cellular host response through deformability cytometry of leukocyte biophysical properties.

The test is designed for use in patients who present at an emergency department with signs of sepsis or who physicians suspect may have infections. Sepsis can be life-threatening, and physicians need to decide quickly whether to start aggressive treatments.

Cytovale has been preparing in recent years the company's entry into the US market with support from the US Department of Health and Human Services and private investors. In the recent run-up to that launch, company officials said in a statement they have been working to secure reimbursement for the test and applied for a Current Procedural Terminology (CPT) Proprietary Laboratory Analyses (PLA) code for IntelliSep.

The firm said it needs to focus its initial commercialization on the US because it is a small company with limited resources. But it plans to eventually sell the test globally.

As with all diagnostics startups, questions will surround how the company will convince clinicians to use its test. Cytovale has noted that IntelliSep is fast and intuitive, and the firm believes its results can help hospitals improve both patient outcomes and resource use. Sepsis is among the conditions with the greatest clinical and economic impact for hospitals, and the absence of clear diagnostics in emergency departments leaves potential for missed sepsis cases as well as unnecessary interventions including hospitalization and antibiotic prescriptions.

The company said a hospital can expect to save $9 for every $1 spent on IntelliSep testing. Cytovale declined to disclose the price of the test but said it will be in line with other tests on the market.

That competition includes molecular assays such as BioMérieux's Biofire panel for pathogens known to cause sepsis, protein biomarker-based procalcitonin tests, and Immunexpress' recently cleared qPCR-based gene expression test. Cytovale is among the many firms that have been working in recent years to bring direct-from-blood tests to market.

The phenotypic and molecular assays available today tend to be laboratory-based diagnostics that require days to get answers because of their reliance on blood cultures that can require 24 to 72 hours. But several other firms are developing tests to identify antimicrobial susceptibility and sepsis utilizing a variety of technologies such as PCR, gene expression analysis, and spectroscopy, which could rapidly speed up the diagnostic process.

For example, Immunexpress began US commercialization this year of its SeptiCyte Rapid test to distinguish sepsis from noninfectious systemic inflammation in about one hour, and it can be used in conjunction with tests such as those measuring procalcitonin and lactate.

Meanwhile, T2 Biosystems has FDA clearance and sells in the US its T2Bacteria panel, which detects five clinically relevant bacterial pathogens in a few hours from a whole blood sample. The test may be used to detect bloodstream infections that could lead to sepsis and guide appropriate treatment earlier.

The American Association of Clinical Chemistry also recently published guidelines that discouraged routine use of PCT tests to predict the 28-day mortality risk in sepsis patients, citing a lack of consistent PCT cutoffs and clearance parameters and insufficient evidence of benefit to patients.

Cytovale also released in May study results it used in support of its 510(k) application. In a poster presentation for the American Thoracic Society International Conference in Washington, DC, the company said that among 572 patients, 79 of 160 patients stratified into the highest-risk category for sepsis developed the disease compared to 45 of 160 in the middle category and 28 of 252 in the lowest category. Emergency department doctors diagnosed sepsis in 52 of those 152 patients who developed the disease and 24 of 420 patients without sepsis.

Hollis O'Neal, medical director of research at Our Lady of the Lake Regional Medical Center and critical care physician at Louisiana State University Health Sciences Center, as well as lead investigator on the study, said the results also showed that the patients identified by the test as having the highest risk also were the most likely to develop severe illness, especially but not limited to sepsis-related disease, and they were more likely to be hospitalized for longer periods compared to patients in the lower risk groups. The lowest risk group, in contrast, had the lowest infection rates, shortest hospital stays, lowest rates of organ dysfunction, and lowest sequential organ failure assessment scores.

O'Neal said emergency department physicians often lack information they need to diagnose infection. He said organ dysfunction can be difficult to predict and it's nearly impossible to assess the dysregulated host response characteristic of sepsis.

"We can give an assessment of this host response and can quantify the host response or the degree of dysregulation that we're seeing, which is the currently understood pathobiology of sepsis."

O'Neal said Our Lady of the Lake's hospital system, the Franciscan Missionaries of Our Lady Health System, is implementing IntelliSep in emergency departments in Louisiana and Mississippi, where IntelliSep results are integrated with medical records and clinicians receive prompts to apply the technology.

"This is meant to serve as an aid in the diagnosis of sepsis," he said. "It's not meant to serve as a black or white 'Yes, if this test is positive, you have sepsis. No, if it's negative, you don't have sepsis.'"

For patients in the lowest risk category, physicians should prioritize searching for alternative diagnoses rather than pursuing sepsis treatment, he said. For the highest, they will be prompted to follow the protocol of treating likely sepsis, including administration of broad-spectrum antibiotics, ordering cultures, and ordering lactic acid treatments. Absent these results, he said more patients without sepsis receive those treatments than those who do.

"We're diverting resources into people who don't have the disease and missing a number of people who do because it's difficult" to diagnose sepsis, he said. "So, our goal of the implementation in our system is going to be the redirecting of those resources into patients who are at highest probability for the disease."

O'Neal said that in the study the median turnaround time for results was under 8 minutes. "Even in this multi-center clinical trial, where techs had never really used this instrument before, we could get a result in under 10 minutes."

Todd Rice, professor of medicine at Vanderbilt University and one of the researchers on the validation study used to support IntelliSep's 510(k) clearance, said diagnosing sepsis typically requires a good clinician and a high level of suspicion, and he and colleagues in emergency medicine have long wanted a diagnostic test that improves on what's available on the market. While Cytovale's test is imperfect, he said, "It's moderately good and it will be another piece of information that clinicians will be able to take into consideration and help them make a diagnosis of sepsis."

Rice said the IntelliSep test also fits into existing hospital workflows because a bedside machine can deliver results quickly from a blood sample.

Test results that show cellular inflammation characteristic of sepsis can help give a clinician higher confidence in their course of treatment for a patient they suspect has sepsis, and results showing low risk can support a decision to send a patient home. While he said the test did moderately well at telling which patients were at risk of developing sepsis, he said it did better at discriminating who would need inpatient medical care because, even among patients who would not develop sepsis, results that indicated high risk provided a warning that they were experiencing some type of harmful event.

"It's a good test and it provides you with useful information that, when you then combine that with some clinical judgment, it's going to help us make better decisions," Rice said.

O'Neal said Cytovale is looking for partners to be early adopters of IntelliSep, and he said those early adopters will further prove the technology can improve outcomes and the efficiency of sepsis care.

O'Neal is involved in two further studies, which are currently enrolling participants, on how the test would be used in different hospital systems and whether the test results change over time. The test is designed for single use, but he said the scores should shift over the course of treatment and help determine whether performance is affected by, for example, a person who presents to an emergency department a day after visiting a point-of-care clinic and receiving a prescription for antibiotics.

O'Neal said the test can help physicians identify not only who to prioritize for treatment but also potentially spare other patients from unnecessary treatments and redirect those efforts, improving the efficiency of sepsis care and outcomes and reducing morbidity and costs. He also expects IntelliSep will help improve the throughput of emergency departments.

"We can deliver care to those patients who are currently not getting the most efficient care – the most effective care – only because it's such a difficult disease to diagnose," he said. "It consumes so many resources."