Curetis Blood Culture CE-IVD

NEW YORK (GenomeWeb) – In preparation for a CE-IVD launch in the second quarter, Curetis has initiated the final performance evaluation of its BCU Blood Culture Application cartridge to diagnose bloodstream infections.

The Holzgerlingen, Germany-based company is also gathering momentum from its November IPO on Euronext to launch additional products and to establish a US operation in advance of potential US Food and Drug Administration clearance of its Unyvero sample-to-answer molecular diagnostics platform and initial test for lower respiratory tract infections.

The blood culture assay is expected to launch in Europe in a few weeks, and will join the company’s existing assays for tissue infections and pneumonia. It is a large panel assay that simultaneously tests for more than 100 pathogens that can cause sepsis.

“We believe it is currently the most comprehensive MDx panel for blood culture testing,” said Achim Plum, Curetis’ chief commercial officer, in an interview.

The launch is also a part of the firm’s strategy to introduce two new cartridges per year and do one “life-cycle management” on an existing application, Plum said, so this year the firm is also planning to launch a molecular diagnostic assay for intra-abdominal infections and a second generation of its test for implant and tissue infections, called ITI.

Like all the firm’s diagnostics, the blood culture test uses the firm’s Unyvero platform and fully-integrated cartridges. Plum noted that Curetis’ overall mission is to focus on syndromic testing, rather than screening, using “large, multiplexed panels that give comprehensive answers for an individual patient.”

The BCU’s more than 100 targets include gram-positive and gram-negative bacteria, fungi, and mycobacteria, plus 16 antibiotic resistance markers. It can enable near-patient testing, reduce overuse of antibacterial drugs, and may be good for smaller hospitals that don’t have in-house microbiology labs, Plum said.

The test is being validated in conjunction with blood culture bottles used on other commonly available systems, including the BD Bactec system and the BioMérieux Bact/Alert, Plum said. Curetis will also be further evaluating the product immediately after launch at three clinical sites to learn about first customer experiences with it, and it plans to officially introduce the BCU cartridge at the European Congress of Clinical Microbiology and Infectious Diseases conference in April.

Flexibility in sample type is a key to the product line, Plum said. The Unyvero system has a separate lysis instrument, called the Lysator, which enables “any thinkable native sample type that comes out of the clinical routine.” The lysis step requires about one minute of hands-on time and 30 minutes of run time. In the same closed tube, the lysated sample is then transferred to the assay cartridge.

Within the cartridge the sample goes through column-based DNA extraction, followed by eight independent multiplex PCRs in eight independent PCR chambers that are fully integrated into the cartridge, with subsequent microarray detection of the PCR products in each chamber.

Overall, results take four to five hours, with around five minutes of total hands-on time, Plum said.

The test also requires no particular molecular biology skill. “That is really important for the adoption of such a system,” he said. “We also want to target labs that don’t have normal PCR capabilities … so it can be operated virtually in any environment, and even outside the lab, [and] we have placed a number of systems on intensive care units or in near-patient settings,” he said.

The BCU assay took around eight months to develop, an amount of time which Plum said is “fairly short for that kind of application.” But the cartridge’s eight-chambered structure allows Curetis “to approach the design in a very modular fashion,” and work on each chamber independently.

The BCU was also developed in response to customers. “We have quite a number of customers who said, ‘We have your system and we would like to use it for blood culture, can’t you develop an application for that?’ so it was very market- and customer-driven,” Plum said.

And, although a number of players — such as BioMérieux’s BioFire Diagnostics, T2 Biosystems, Qvella, Biocartis, and Atlas Genetics — are targeting the blood infection space, Curetis has an advantage in the size of its panel, the number of resistance markers evaluated, and the ability to work with multiple sample types, in this case different blood culture bottles, Plum said.

In addition, Curetis has been developing a host-response panel licensed from Accumen Research Laboratories of Singapore that may also help address the low levels of pathogen and transient spikes sometimes seen in sepsis. That test looks at markers in peripheral blood lymphocytes to detect whether there are pathogens present and whether there is a systemic inflammatory response syndrome. The firm’s timeline for this test to be ready is “not before the end of 2017,” Plum said.

For sepsis, the firm is not as interested in direct molecular detection from patient blood samples, however. “We’d rather focus initially on blood culture as one way of addressing sepsis, where basically the blood culture is a pre-amplification of the sample,” Plum said, adding that the firm would look to later develop the sepsis host response test, “where we use the immune system of the host as an amplifier of signal.”

The firm is also developing an intra-abdominal assay that it plans to launch toward the end of this year. It is adding analytes for a second generation of its implant and tissue infection cartridge expected in Europe mid this year, and it launched a second-generation pneumonia cartridge last year.

The ITI has “a very good response from the market, in particular for prosthetic joint infections because these create quite a significant health economic burden,” Plum noted. It is also useful for seven other applications, such as catheter, surgical site, and cardiac infections, and burn wounds.

Path to the US

Curetis is “well under way with enrollment” for a significant US trial of the Unyvero system and a pneumonia cartridge, which is called P55 in Europe but will be re-named the Lower Respiratory Tract Infection cartridge in the US.

The firm plans to submit to the US Food and Drug Administration in the second half of this year.

“With the usual regulatory timeline for the 510(k) for the instrument and de novo 510(k) for the application, that puts us on a timeline for launch hopefully in the first half of next year in the US,” Plum said, adding, “We will be providing regular updates on the progress of the trial because it is obviously something that is quite important to the company [and] so far we are on track for that timeline.”

To speed this process, Plum has initiated a search for the general manager for Curetis’ future US operations.

“Once we have that person on board, our plan is to have a core team, like a handful of people, operational in the second half of this year to prepare the launch,” he said.

The firm plans to go direct to the US, rather than address the US market through partners, because “it is the most important market and you’d like to keep full control of the commercialization and introduction, and also capture the margin there,” he said.

Curetis’ target customers are labs in “sizeable hospitals with sizeable intensive care units or appropriate specializations, like orthopedic,” and this will be the same sales channel it expects to build in the US.

This is a “reasonable number of sales targets” in the US, perhaps a couple hundred, he said, and Plum expects a core team of three or four people hired now to bring on board about 20 sales reps and application specialists in time for launch in order to cover the US.

In the wake of its IPO, which netted the company €40 million (about $42.8 million at the time), Curetis is also beefing up its commercial team in Europe. It recently hired Willem Haagmans, a former general manager in the Netherlands for Beckman Coulter, as new head of sales for the Europe, Middle East, and Africa region.

“At the moment we are hiring about ten further people in the commercial team — sales people, application specialists, scientific affairs managers — to really help fast track the commercialization in Europe,” Plum said.

The company is also seeking additional distribution partners in geographies that it doesn’t yet cover, recently signing a deal in China, as well as one covering countries that are part of the Association of Southeast Asian Nations which will initially include Singapore, Malaysia, Thailand, and Indonesia.

By the end of last year Curetis had placed 42 systems in the direct selling market and 24 systems in the US for the clinical trials, Plum said. “The total installed base at the end of last year … that were either placed by us or bought by distributers was 103 systems,” he said, with 37 of those sold to distributors.

The Unyvero platform has a list price around €60,000 (US$65,743), although the majority of systems are placed as reagent rentals. Typically, the cartridges are in the €200 range, with the pneumonia assay costing €192, and ITI available for €272, Plum said.