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Newsletter Vol. 29 No. 2




Tackling Urgent Needs in Infectious Disease Testing: an interview with Curetis AG

Gerd Lüdke, Ph.D.
Director of Bio-Assay Development
Curetis AG

 




Curetis AG (headquartered near Stuttgart, Germany) is a molecular diagnostics company focusing on the development, clinical validation, and commercialization of solutions for easy-to-use, fast, and reliable molecular infectious disease testing.

What led you to focus on the pneumonia application first?

Pneumonia is a high incidence disease with hundreds of thousands of cases each year and a high unmet medical need for more accurate and rapid diagnosis. The disease causes a huge economic burden on healthcare systems and on society at large, with mortality rates of up to 36% and an average hospital stay of 11 to 14 days. Culture-based diagnostics of bacteria and antibiotic resistance is the current gold standard for diagnosis of pneumonia. However, this typically takes at least two to three days – far too slow. Because of missing diagnostic information most initial pneumonia therapies rely on empiric decisions, which lead to high rates (about 40%) of initially inadequate antibiotic treatments. Inadequate treatment and the widespread use of broad-spectrum antibiotics support the development of antibiotic resistance. Studies have shown that an early adequate and targeted treatment can significantly reduce both mortality and the length of hospital stays. Faster diagnosis could help rule out infection with certain pathogens earlier. In the future this might enable a faster adjustment of antibiotic therapy, and could support other efforts to stop the vicious cycle of rising antibiotic resistance.

Many companies are trying to enter the infectious disease market - what is unique about your company’s team approach?
The development of novel diagnostic devices is frequently driven by a “technology-out” approach that does not always focus squarely on clinicians' and users' unmet needs. Many products building on so-called “breakthrough technologies” have fallen short of their great promise. With our cross-functional team of engineers, scientists, physicians, marketing, supply chain and manufacturing experts we have chosen a “market-in” approach instead: our R&D program has been designed to specifically target customer needs by integrating and automating several existing, well-established and proven technologies. The result is a closed, walk-away, easy to use platform (the Unyvero System), which once validated in clinical trials and cleared by the FDA would enable 24/7 testing – not only in microbiology core laboratories but also in near-patient settings. The Unyvero Pneumonia Application has been designed for the simultaneous detection of 17 pathogens and 22 antibiotic resistance markers at reasonable cost. Producing relevant diagnostic results in three to four hours rather than several days not only helps save patient lives and reduce ICU days, but might also be cost-saving from a hospital's point of view.

What technical challenges did you face in developing your novel applications (the Unyvero platform and Pneumonia Application)?
The Curetis team has learned from extensive global market research studies and key opinion leaders that a new testing solution would have to handle a comprehensive marker panel for bacteria and antibiotic resistances. Such a panel would need to cover more than 90% of all disease-causing bacteria. In the case of pneumonia, epidemiological data from multiple hospitals in the US and Europe has shown that this requires analyzing roughly 40 genetic markers from a single patient sample simultaneously. This presents a veritable challenge linked to mainly two obstacles: the heterogeneity of the clinical sample types, and the lack of understanding of the predominant antibiotic resistance mechanisms for certain pathogens at a molecular level. During the last four years, we have worked out a truly novel, unique, and rather simple pre-analytics approach to handling all clinically relevant samples types. Our Unyvero Lysator can handle challenging materials, like highly viscous sputa, just as easily as tracheal aspirates, BAL (bronchial alveolar lavage) samples, blood, urine and many others.

For the purposes of analytics, it was also essential to develop an in-depth understanding of the underlying genetics. We have identified what we believe are the best markers for potential antibiotic resistance. However, we will need to carefully demonstrate their clinical relevance in prospective clinical trials for a future FDA filing. Altogether this will require extensive testing of thousands of isolates in clinical trials planned for later this year.

Do you see clinical and regulatory challenges for your products?
The demand to cover not only clinically relevant, but also rare pathogens found in various clinical sample types requires large numbers of patient samples during clinical testing. Such clinical validation is complicated by the fact that microbial culture is a rather poor “gold standard.” Peer-reviewed studies have demonstrated the limitations of traditional culture methods. Currently there is no single FDA-cleared platform or assay for highly multiplexed bacteria and antibiotic resistance marker detection available. Therefore we have decided to initiate an extensive, prospective international multi-center clinical trial in Europe and the US to validate our Pneumonia Application's performance compared to the culture-based standard of care.

However, obtaining regulatory clearance by no means ensures future market success. Users, physicians, hospital administrators and payors demand comprehensive demonstration of product performance and a potential for improving medical and economic outcomes. Clinical trials and development programs focusing on post-marketing trials are essential, but time-consuming and expensive – a challenge for venture-backed companies such as Curetis.

How do you envisage building market-acceptance for your products?
Building acceptance for molecular testing is a challenge that affects healthcare industry, practitioners, and patients. We hope to use expert opinion to increase public awareness and address the gaps in knowledge concerning the importance of rapid pathogen and simultaneous antibiotic resistance marker detection. Every new platform and approach in molecular diagnostics today faces preconceived notions based on the incomplete understanding of infectious diseases and their underlying genetics, and of antibiotics prescription philosophies. High quality, well-designed clinical studies conducted at centres with reputations of excellence will help convince the broader medical community of the clinical value of any new technology. In this quest, the molecular diagnostics industry needs to work hand-in-hand with societies like APUA towards the common goal of saving patient lives and at the same time reducing healthcare costs by faster, more accurate and comprehensive diagnoses.

To date neither the Unyvero Solution nor the Unyvero Pneumonia Application have been validated in clinical trials, nor have they been cleared by the FDA; products are currently not available for sale in the U.S.
 




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