By Ben Butkus
German molecular diagnostics firm SIRS-Lab this week commenced a 1,000-patient clinical study in its home country to evaluate Vyoo, the company's PCR- and microarray-based molecular test for causative agents of sepsis.
Results from the trial, which will support an application for regulatory approval in Europe, will be available in 2012, at which point SIRS-Lab will also contemplate seeking 510(k) clearance in the US, a company spokesperson said this week.
In the meantime, results from the clinical study will help support SIRS-Lab's recently announced collaboration with Pfizer focused on sepsis diagnosis and treatment.
SIRS-Lab was founded in 2001 out of University Hospital Jena to commercialize a sample prep system that concentrates pathogen DNA from complex samples such as whole blood, a product that the company eventually commercialized in 2005 with the brand name Looxster.
The company then began integrating Looxster into the Vyoo molecular test to rapidly detect sepsis-causing pathogens from whole blood. The original version of Vyoo combined quantitative real-time PCR of multiple sepsis-causing pathogens with gel electrophoresis analysis, and received the CE Mark in late 2008.
However, soon thereafter, realizing the importance of speed in sepsis testing, the company switched gears and began developing a version of Vyoo that combined highly multiplexed qPCR with microarray analysis to identify molecular signatures of a variety of pathogens implicated in sepsis.
"We switched to an array because it is much more objective and easier to handle," Axel Kunz, a corporate communications officer at SIRS-Lab, told PCR Insider this week. "You get a clear result and don't need to interpret a gel. This is clearly demanded in the market and also reduces hands-on time. So overall, an array has many advantages in precision, handling, [and] security [over] a gel."
The current version of Vyoo begins with whole blood from patients; uses SIRS-Lab's Looxster and other enrichment technology to isolate and purify DNA; then seeks the molecular signatures of 34 bacterial and seven fungal species, and five genes for antibiotic resistance.
"We have developed primers for all of those targets; we [have] a closed system [which is] especially important for sepsis; and we have 99 percent of all possible sepsis pathogens, and also five resistances in the run, which is important if you want to address antibiotics later," Kunz said.
"Because it's PCR-based means that it takes about 7 hours for one run, and then you get the results," Kunz added. "In the end, the software just tells you, 'OK, these are the genes you have, and that's the [antibiotic] resistance.'"
The PCR portion of Vyoo can be run on just about any standard laboratory thermal cycler, Kunz said. The microarray readout analysis is performed on an ArrayMate platform provided by German life sciences firm Alere, which was formerly known as Inverness Medical Deutschland.
Kunz also noted that Vyoo necessitates the use of various platforms for cell lysis and nucleic acid enrichment. "We recommend certain instrumentation, but this of course is flexible," he said.
SIRS-Lab also has in place a partnership with Analytik Jena, which provides a platform and associated reagents for automated isolation of nucleic acids for the Vyoo test (PCR Insider, 6/17/2010).
In November SIRS-Lab announced its plans for a large-scale clinical trial to evaluate the new version of Vyoo, and this week, the company said it has enrolled its first patient.
Led by Tobias Welte, president of the German Sepsis Society, the 1,000-patient clinical study will be performed in 11 centers across Germany, mainly university hospitals with medical microbiology laboratories, the company said.
The goal of the trial is to compare the sensitivity and specificity of Vyoo with current standard blood culture and clinical diagnosis procedures used at hospitals. More specifically, it will "evaluate how Vyoo supports the clinician's decision making and delivers critical information to support early and targeted anti-infective therapy," the company said in a statement.
Kunz added that although SIRS-Lab had received the CE Mark for the previous version of Vyoo, "now that we have the microarray we need a new CE Mark. And of course, part of the goal of this study is that CE Mark. The most important thing, of course, is just to prove that it works and that the data has an advantage over traditional blood cultures and actually brings an advantage in the ICU."
Seeking approval from the US Food and Drug Administration is a much longer-term goal for the company, Kunz said.
"I'm not sure about US yet. I think the first step for us is Europe. On the other hand, we have talked to the FDA already, and once we have the data, we can decide to approach that. But we are a small company, so we are remaining very focused."
For now, the market for a rapid, point-of-care, molecular test for sepsis remains relatively untapped, although other companies are beginning to make progress in developing such an assay, even in SIRS-Lab's home country.
For instance, just this week Korea's Seegene announced that it will partner with Germany's Molzym to develop an automated sepsis test using Seegene's Magicplex technology, which purports to be able to identify more than 90 sepsis-causing pathogens (related story, this issue). Under that partnership, Molzym will supply microbial DNA-enrichment technology.
In fact, it appears that the POC sepsis-testing market is particularly active in Germany, as companies such as Eppendorf and Magna Diagnostics are considering sepsis as an initial application for their multiplex PCR technologies (PCR Insider, 11/11/10 and 1/6/10).
However, SIRS-Lab has a powerful ally in its corner: Pfizer, which is collaborating with the German firm to evaluate the clinical impact of using molecular tests for diagnosing severe fungal bloodstream infections, as well as the pharmacoeconomics of such an approach, SIRS-Lab said in November.
As Kunz sees it, multiplex molecular testing for sepsis is clearly the way of the future, although hurdles remain.
"I think the multiplex thing is still one of the biggest challenges, to make sure there isn't cross-talk [or cross-reactivity], but we have seen that our platform works," he said.
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