NEW YORK (GenomeWeb) — German molecular diagnostics firm Curetis today received CE-IVD marking for an updated version of its highly multiplexed pneumonia molecular testing panel, setting the stage for an official rollout of the product at the European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) meeting later this month.
Meanwhile, the company is pushing ahead with a clinical trial designed to generate data to support the test's approval in the US, with the goal of submitting a regulatory filing to the US Food and Drug Administration in the second half of 2016.
Curetis' core product is its Unyvero Analyzer, an automated benchtop nucleic acid testing platform that combines a proprietary universal sample prep method with endpoint PCR and array-based detection.
The company already has two test cartridges for the system on the market in Europe including P50, which simultaneously analyzes 39 DNA targets to detect 16 bacteria and one fungus associated with non-viral pneumonia, as well as 22 antibiotic resistance markers.
Curetis is now set to roll out the successor to that test called P55, which detects 21 pathogens including the new targets Mycoplasma pneumoniae, Citrobacter freundii, Enterobacter aerogenes, and Klebsiella variicola. P55 also includes new antibiotic resistance markers including genes coding for carbapenem and oxacillin resistance.
Early last month, Curetis announced that it had begun clinically evaluating the P55 cartridge, comparing its specificity and sensitivity to microbiology culture. Having completed that study, the company just today signed the declaration of conformity for CE marking, CEO Oliver Schacht told GenomeWeb.
The formal launch of the test, however, is set for April 25 at the ECCMID event in conjunction with the presentation of the clinical and analytical validation data, which were generated from more than 800 cartridge runs and over 400 patient samples.
Schacht noted that the company also has data from several hundred additional patients samples, which will be included in an upcoming publication of the data released at the ECCMID meeting.
At the same time, Curetis is working to get the pneumonia test cleared for sale in the US, although Schacht noted that it would be called LRT55 — shorthand for lower respiratory tract — after the FDA requested that the firm not use the P55 moniker.
The agency, he said, was concerned that the original name implied pneumonia even before the test had been run to confirm such an infection.
The US trial, which began in mid-2013, was originally evaluating the P50 panel, but has since been amended to examine the updated P55 test. Schacht also said that the study's protocol has been changed to account for recent guidance from the FDA on the development of in vitro diagnostics.
"The FDA has given companies in this space … the opportunity to effectively run two studies" to gain approval for their tests, he explained. "One, which [includes] a minimum of 1,500 samples prospectively collected at multiple sites, is only for specificity. The agency allows companies to do their clinical sensitivity analysis from retrospectively collected specimens. We've evolved our trial design to reflect that."
Schacht said that Curetis and its collaborators have been collecting hundreds of clinical samples where the microbiology data are known in order to get to a sufficiently large number of cases to provide sensitivity data for each pathogen on the panel.
"In parallel, [we're going to] run 1,500 samples prospectively for specificity," he said. The company hopes to complete the study by mid-2016 and submit it for approval shortly thereafter.
He added that an approval of LRT55 would also include clearance of the Unyvero system itself, laying the groundwork for additional test cartridge approvals. The nature of the company's second assay for the US market, however, remains unclear.
In addition to P50 — soon to be replaced by P55 — Curetis sells in Europe a Unyvero cartridge called i60, which identifies more than 90 pathogens and more than 20 resistance markers common in implant and tissue infections.
Although the company could choose to pursue FDA approval for this test, the regulatory landscape in the US complicates such an effort, Schacht said.
The i60 detects 23 resistance markers and 91 pathogens, and covers eight different clinical indication areas including infections associated with implants, catheters, surgical sites, and burn wounds. The test also works with a range of sample types such as synovial fluid, biopsy material, and bone cement.
According to Schacht, the FDA would require the company to run separate clinical studies for each indication and sample type.
"Given the breadth of this panel, with up to 114 analytes, that almost becomes an exercise in impossibility," he said. "This ends up becoming a trial of several tens of thousands of patients. Honestly, very few folks in diagnostics would run those types of trials."
To pursue a US launch, Curetis would instead have to run a study focused on one indication and one or two sample types. Once that is approved, the firm would have to repeat the process again and again.
While that remains an option, Schacht said Curetis is also considering making a blood infection test called B70 its second US offering.
That assay is currently under development, but the company anticipates moving it into a clinical validation trial in Europe in the fourth quarter, with CE marking coming as soon as the end of the year.
A decision on whether Curetis will move ahead with B70 or i60 in the US, Schacht said, will likely be made in the first half of 2016.