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T2 Biosystems Counting on Bacteria Panel Trial Results to Support Adoption of Broader Dx Portfolio

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NEW YORK (360Dx) – T2 Biosystems is counting on the publication last week of a pivotal clinical trial to educate clinicians and drive adoption of its direct-from-blood instrument and tests.

The recent publication of the pivotal clinical study for its T2Bacteria panel in the Annals of Internal Medicine is an important milestone for T2 Biosystems, Tom Lowery, the firm's chief scientific officer, said in an interview.

The study showed strong performance data, including "high sensitivity and high specificity and demonstrated the quality of results direct from blood in a first-of-its kind test," he said.

Further, the study demonstrated the "novel clinical impact that is possible from use of the test, such as being able to detect bloodstream pathogens that are missed by blood culture," Lowery added.

About a year ago, the US Food and Drug Administration granted clearance for the T2Bacteria panel, which uses magnetic resonance technology to detect bloodstream infections, such as sepsis, directly from a blood draw. Since then, the firm has been placing bacterial tests in hospitals interested in using them for diagnostic stewardship, and testing in intensive care units and emergency departments, among other settings. The firm's first tranche of customers for the T2Bacteria panel is beginning to use the test on patients after completing validations.

In the multi-center study that preceded FDA clearance, 11 US hospitals tested the clinical performance of the panel. Having enrolled patients from December 2015 through August 2017, investigators collected blood specimens from 1,427 patients who had ordered a blood culture — the gold standard for diagnosing bloodstream infections — as part of the standard of care.

In the pivotal trial, the T2Bacteria Panel consisted of common bacteria, known as ESKAPE pathogens — Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumonia, Pseudomonas aeruginosa, and Escherichia coli — that are the most likely to escape or resist effective antibiotic therapy.

Blood cultures took between 32 and 111 hours to identify pathogens, while the T2Bacteria panel took between 3.6 and 7.7 hours to accomplish the same task.

The T2Bacteria panel had a 99.7 percent negative predictive value, an overall sensitivity of 90 percent per subject and per assay, and an overall specificity of 90 percent per subject and of 98 percent per assay.

Because the instrument enables an advance in clinical practice and removes blood culturing, a step in testing that slows results, clinicians need to think of how to best integrate the T2 Biosystems instrument and its assays into their clinical algorithms, Cornelius Clancy, chief of infectious diseases at the US Department of Veterans Affairs Pittsburgh Healthcare System and an author of the T2Bacteria pivotal study, said in an interview.

"Clinical teams are going to have to think about how to best integrate these tests into stewardship practices to realize the maximum benefits from them," he said.

Direct-from-blood assays, such as those enabled by the T2 Biosystems magnetic resonance instrument, "clearly provide clinical utility" because they address the unmet need of providing a rapid test result in clinical situations that need it, Clancy said.

Reducing the time it takes to get results from a blood culture measured in days to direct-from-blood testing time measured in hours enables clinicians to address life-threatening infections, such as sepsis, that require rapid diagnosis, and clinicians have been waiting for something like this for years, he said.

While careful and selected placement of the instrument and its assays is vital for hospitals, given potential clinical benefits, many clinicians may thus far be unfamiliar with how to best implement it in clinical practice, he said.

Although ramping up revenues for the T2Bacteria panel is just beginning, the publication of the pivotal clinical trial is likely to drive marketing awareness, and in some respects put T2 Biosystems on the map, Canaccord Genuity analyst Mark Massaro said in an interview.

Similar to the way in which the publication of a pivotal trial for Exact Sciences' Cologuard test helped raise that firm's profile, the publication associated with T2 Biosystems' bacterial panel "will certainly help drive sales," Massaro said.

Cologuard, a molecular test that detects colorectal cancers and pre-cancers from a stool sample, received premarket approval from the FDA in August 2014, and results from Exact Sciences' prospective 90-site, point-in-time, 10,000-patient pivotal trial were published in the New England Journal of Medicine in March 2014.

Massaro noted that with the publication of its trial, T2 Biosystems can now ramp efforts to build its installed base after its T2 Candida panel, cleared a few years ago by the FDA, had fallen short of initial expectations for placements and revenues.

The market opportunity for selling the bacterial panel far exceeds that of the fungal panel, he said, adding that it is clear that fungal infections are far less common than bacterial infections. Prevalence varies by institution, but fungal infections can present between 1 and 20 percent of the time as a cause of bloodstream infections, leaving a far larger market for testing of infections caused by bacteria, he said.

Further, many physicians who took a pass on the Candida panel or adopted a wait and see approach may now be ready to purchase the T2Bacteria panel, he said, adding, "I believe that a large number of institutions were waiting for the bacterial panel to come on the market, and now that it's here I certainly expect adoption to rise."

Lowery noted that peer-reviewed scientific literature and other studies presented separately by Clancy and scientists from other health centers at the European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) in Amsterdam should also help drive adoption.

Some principal investigators have been awaiting the publication of the pivotal bacterial panel study before submitting their own data for publications that involve studies demonstrating the clinical utility of the test, he said.

Clancy noted that in more than two years of using the T2Candida panel at the VA Pittsburgh Healthcare System, he and his colleagues have mapped a way to identify patients for whom the tests offer the most value, and applications that enable clinicians to make the most rational treatment decisions. He said that he anticipates clinicians will undertake a similar approach when applying T2Bacteria and other future panels running on the firm's instrument.

It's important to note that the instruments and assays can't be "used indiscriminately on all patients in the hospital with a bloodstream infection," he said. Blood culture, despite drawbacks in time to result for some applications, will always coexist in clinician practice with new tests introduced for specific purposes, he noted.

Clancy, along with M. Hong Nguyen, also a contributor to the recent bacterial pivotal trial paper, have been using the T2Candida test within their diagnostic stewardship team, and they are getting ready to roll out the T2Bacteria panel in clinical practice using an approach similar to the one they employed in the use of the T2Candida panel — evaluating and prioritizing its most important uses.

In the stewardship team's diagnostic algorithms, the T2 instrument and panels haven't replaced other tests, but they occupy their own place in clinical workflows, Clancy noted.

That has enabled the hospital to achieve two important objectives — do a better job treating patients with Candida infections and make more rational use of antifungals, Clancy said.

Invasive candidiasis is a "major clinical problem" in intensive care units, and patient outcomes are bad, he noted. In these clinical circumstances, physicians generally overprescribe preemptive antifungal agents, and implementing the T2 tests is part of the overall effort to manage that in his institution.

In the units in which they rolled out the T2Candida panel, he said, they've achieved a 47 percent decrease in antifungal consumption.

Both Lowery and Massaro separately noted that the firm's work on developing a panel that detects resistance genes associated with antibiotic resistance should pay off through increased demand for its products.

In late February, the FDA granted Breakthrough Device Designation for its T2Resistance Panel that can detect 13 resistance genes from both gram-positive and gram-negative pathogens and from a single patient blood sample without waiting for a blood culture.

The firm anticipates launching the T2Resistance Panel for research use in the US and commercially outside the US later this year.

Lowery said he believes "the first ever data" for use of a direct-from-blood, ultra-high sensitivity for resistance markers using the firm's T2Carba Resistance+ panel was presented in April at ECCMID.

During the presentation, Giulia De Angelis, a researcher at the Institute of Microbiology, Università Cattolica del Sacro Cuore in Rome, said that direct-from-blood resistance gene detection of gram-negative bacteria in patient samples using T2's resistance panel showed accurate detection of Klebsiella pneumoniae carbapenemase and other resistance markers in patients samples about 5 hours from blood draw."

These results were obtained "multiple days faster" than with standard-of-care blood culture-based testing there, Lowery said.