NEW YORK (GenomeWeb) – German molecular diagnostics firm Curetis has successfully completed a large clinical trial of its lower respiratory panel (LRP) in anticipation of submitting the panel and its Unyvero system to the US Food and Drug Administration by the end of the year.
The panel is designed for critical lower respiratory tract infections, which are often diagnosed as pneumonia, and detects 21 different pathogens and 19 resistance markers, Curetis' CEO Oliver Schacht told GenomeWeb in an interview. It is currently CE-marked in Europe, where it is known as a pneumonia panel.
The US trial yielded data on each one of the 40 individual diagnostic targets, but taking all the data together and looking at weighted averages of all the analytes led to a sensitivity and specificity of approximately 90 and 99 percent, respectively.
"This US FDA trial has comprehensively and conclusively validated the clinical performance data of the European product that we've had for the last couple years," Schacht noted.
The panel was compared to both microbiology and individual PCR testing plus sequencing. Schacht noted that the panel was not compared to another commercial test, because "frankly, there is no commercial test available today that would cover all these pathogens and resistance markers."
Microbiology is not the ideal gold standard test, however, as sometimes pathogens don't grow in culture. So, the FDA required Curetis to compare the LRP product against culture, but also required that culture-negative samples be evaluated with PCR and sequencing. The combination of these comparators was used to determine overall sensitivity and specificity.
The trial was performed at nine sites in the US: Beaumont Health in Michigan, Columbia University, Johns Hopkins University, the Mayo Clinic, Northwestern University, Summa Health in Ohio, the University of California Los Angeles, the University of Rochester, and the University of Washington.
Overall, 2,203 prospective and retrospective tracheal aspirate and bronchoalveolar lavage samples were analyzed, with a total of 5,694 Unyvero Cartridges processed.
Curetis has been planning to bring the lower respiratory panel to the US as its first cleared test on the Unyvero platform, the firm told GenomeWeb earlier this year.
The firm will then pursue clearance for other cartridges on the system. These include its BCU Blood Culture Application test, which simultaneously detects more than 100 pathogens that can cause sepsis, an assay for intra-abdominal infections, and an implant and tissue infection cartridge.
The Unyvero system provides results in four to five hours, with around five minutes of total hands-on time. It has a separate lysis instrument which enables lysis of many different types of clinical samples with about one minute of hands-on time and 30 minutes of run time. The lysated sample, in the same closed tube, is then transferred to an assay cartridge for column-based DNA extraction followed by eight independent multiplex PCRs in eight PCR chambers, with subsequent microarray detection of the PCR products in each chamber.
Although Biomerieux has been developing a lower respiratory panel, there are currently no panels cleared by the FDA or even on the market in Europe, Schacht said.
"Everybody will need to run a large, prospective, multi-center FDA trial," he noted, adding, "I would certainly anticipate that by the time we hopefully get this cleared by the FDA, this will be a first-in-class product ... we're going to see how long we will enjoy a period of being the only one before competitors start catching up."
Other potential competition might come from firms like MDx panel manufacturers GenMark and Nanosphere, or Accelerate Diagnostics' phenotypic approach, Schacht said, but he noted that lower respiratory panel development is not trivial.
"You need a very broad panel ... and you need a very high-performing sample preparation because this is a much more complex patient sample than a nasal swab," he said. The samples are "gluey, clumpy, and sticky," and can present in a range of consistencies, from liquid to "like super glue."
However, the anticipated market for the test is large and it will address a need that is currently unmet.
There are approximately one million patients in the US each year hospitalized with severe pneumonia. At the current European pricing of $200 per cartridge, this would be a $200 million market, but pricing in the US could be different and it is not unusual for diagnostic products to be somewhat more expensive in the US than in Europe, Schacht said.
"It is definitely a very attractive market opportunity, and the same holds true for the other pipeline indications," he said.
The firm plans to target US hospital labs that diagnose critically ill patients. These include major university hospitals, large community hospitals, and large, integrated hospital networks, Schacht said.
Today, clinical routine misses the pneumonia-causing pathogen in somewhere between 25 to 30 percent of cases, and culture takes at least two days, he said.
"For several days clinicians are forced to use broad-spectrum antibiotics empirically, without any diagnostic information," Schacht said. That is often inadequate for the patient, leading to longer stays in intensive care and higher mortality, but it also costs the hospitals money.
"There is a huge economic pressure on US hospitals, specifically for the area of pneumonia," Schacht explained, citing a Centers for Medicare and Medicaid penalty whereby higher-than-average pneumonia readmission rates can lead to three percent cuts in all CMS reimbursement to a given hospital.
Previously-penalized hospitals would be "obvious and logical targets" for the Unyvero system initially, Schacht said.
"Here's something that can help you get a good diagnosis of your patient, get them the right antibiotic, hopefully get the patient out the door quicker, but also make sure they don't come back, which saves the hospital money," he said, the latter because the hospital preserves margin under the cap for the diagnosis-related group.
Curetis designed Unyvero "so that a tired nurse could operate it at three in the morning without thinking about it too much," Schacht said. In Europe, it is installed in centralized microbiology labs as well as decentralized "point-of-need" locations, such as in intensive care units or outside of operating theaters.
However, in the US a decentralized system would likely require CLIA waiver, so Schacht said initially the system will be based in labs in major US hospitals and declined to speculate on whether the firm might seek waiver in the future.
Curetis is now building up its US organization in anticipation of clearance of the Unyvero system and LRP.
"We've put together a core team of a handful of senior executives on the marketing and sales side, building a commercial infrastructure in marketing, sales, clinical and scientific affairs, and the regulatory arena," said Schacht.
The firmed established a US base in La Jolla, California and hired Chris Bernard as president and CEO of Curetis US, Inc. Bernard has a more than 20-year history in the molecular diagnostics space, including many years at Abaxis' point-of-care division, and he has been instrumental in hiring several other senior executives. "He's put the old band back together, as he would say — some of the team he's brought on used to work with him and both Abaxis and Cytyc, so this is a very experienced team who has done this very successfully more than once," Schacht said.
The firm is planning to hire an additional 20 to 25 people once it gets close to FDA clearance. If everything aligns as planned, there is a chance for a first-half 2017 decision, Schacht said, and new hires will also then include 10 to 15 commercial sales people, plus technical support, and a little bit of back office staff for warehousing logistics and shipping product.
The system is currently manufactured by an OEM in Germany, and the cartridges are built at Curetis. Schacht said that for the first few years after launching in the US the firm will continue manufacturing exclusively in Germany and shipping to a central warehouse here, but down the road it consider putting a second cartridge manufacturing facility in North America or Asia.
But completing the clinical trial of the LRP "was one of the key major milestones that we laid out at the IPO in November last year, and here we are, less than a year later, having completed it on time with really great clinical data," Schacht said.
"I think fundamentally this has been a great step in de-risking the regulatory pathway towards the US, so we're really excited and want to get our product to the US market as quickly as we can," he said.