Rebekah Jordan sits down with Oliver Schacht, CEO of OpGen, to discuss the increasing prevalence of antibiotic resistance in Urinary Tract Infections (UTIs), and how OpGen’s Unyvero can quicken the AR diagnosis process.
Key insights:
- UTIs are probably up to 10 million a year, in the US alone, the majority are found in nursing homes and long-term care facilities.
- OpGen released the Unyvero Panel to tackle the rise in AR in an underserved market - a broad panel that is simple to use, and diagnostic results are produced within five hours.
- The Unyvero Panel tests for a totality of 101 different pathogens and antimicrobial resistance markers.
- There is a need for urgency in antibiotic treatment. To tackle broad spectrum antibiotics and thus, antibiotic resistance, a more targeted and personalised approach needs to be taken.
Background
Back in 2007, Curetis started out with an idea of developing a "simple to use, throw in a sample, walk away, get an answer in a closed cartridge-based system.”
“Originally the first product we developed was for pneumonia, then we delved into implant and tissue infection, prosthetic joint infections and bloodstream infection panels. And as we were expanding our menu, we asked ourselves clinically: where do the most severe infections come from? And the one that everybody's ultimately scared of is sepsis,” Oliver said.
20% of bloodstream infections originate in the urinary tract with no sample to answer solutions, to-date, for urinary tract infections. OpGen and Curetis saw this as an opportunity to jointly seize an “underserved market.”
Originally, OpGen had developed a similar PCR panel to Unyvero, however it was on an open platform. Therefore, it was discontinued.
“The Unyvero Panel was chosen as the go ahead, due to the reasons that it was a broader panel and simple to use."
OpGen’s Unyvero Urinary Tract Infection (UTI) Panel works by testing for a broad range of pathogens as well as antimicrobial resistance markers directly from native urine specimens. In the words of Oliver: “Simple as: you drop in a sample from a urine specimen, and you get the full result within five hours.”
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Aim of Unyvero
“We launched it back in Europe and then decided to take it through a prospective multi-centre clinical trial here in the United States towards an FDA submission and ultimately FDA clearance.”
For definition purposes, a panel is the totality of all of those bacteria, fungi and antimicrobial resistance markers that you test for in a sample.
“If you look at a cartridge Unyvero test, it is a physical plastic cartridge. Within that cartridge from a single patient sample, in the case of urinary tract infection, a totality of 101 different pathogens and antimicrobial resistance markers are tested for.”
If you compare this panel to MRSA testing whereby only one pathogen or resistance marker is tested, the advancements are apparent.
Oliver went on to say that the idea of Unyvero was not to provide a test for all UTIs, instead it’s geared towards “moderate volume, but severe cases.”
“In the US alone, UTIs are probably up to 10 million a year, the majority are found in nursing homes and long-term care facilities. What we are really focused on is those 1 to 2 million UTI cases per year that are either very severe, complicated, chronic or recurring. Often these patients are hospitalised and can contract urinary tract infections which can be associated with a catheter for example, which can ultimately lead to things like urosepsis.”
Targeting a specific problem with a generalised solution
Antibiotic resistance (AR) has been around for as long as antibiotics have been around. However, it is increasingly on the rise due to prescription courses of “broad spectrum antibiotics”.
“The thing that has made it worse and continues to make it worse is the fact that we're using broad spectrum antibiotics which, as the name suggests, act very broadly against many different pathogens, so they're not targeted or specific.”
Each time you give a dose of broad-spectrum antibiotics to a patient that has an infection, the bacteria may become resistant to such a drug, which is where you get antibiotic resistance. Usually this is the course of action taken when the underlying pathogen is unknown.
To put this into context, Oliver highlighted the need for urgency in antibiotic treatment.
“We know that microbiology culture, which is still today's gold standard in a lab, takes two to three days, but sometimes can take up to a week or more. So if a doctor has a patient who may be critical, they are faced with a dilemma.”
“Knowing they won’t get an answer from the lab for several days, the doctor is forced to use their best judgment. So they prescribe an empiric dose of broad spectrum antibiotics, knowing that while it may help that one patient, it will also compound and aggravate the problem of ever growing antimicrobial resistance. And this is an ongoing problem for doctors in the current healthcare landscape.”
OpGen hopes to combat this with the quick response of the OpGen Unyvero UTI panel, receiving diagnostics in under five hours. As soon as the pathogen is identified, a targeted and more personalised approach can be taken.
“Once you know what the underlying pathogen is, you can then reassess your decision. Do I really need the broad spectrum? Can I go narrower, more focused and more targeted, and thereby preserve antibiotics as a class of drugs to remain effective for as long as possible?”
Hopes for the future
As for plans to develop the panel further, Oliver explains that the Unyvero design is such that it covers “about 95% of all potential infections.”
When developing a panel, Oliver noted that it should be a “wide to narrow approach”.
“Start out with a very broad panel, again, covering over a hundred pathogenic species and resistance markers. As new resistance mechanisms emerge, the panel should be changed and adapted accordingly.”
From a regulatory standpoint, as true for the IVDR (in vitro diagnostic regulations) in Europe and the FDA in the US, you would need to run a new clinical study performance, evaluation, resubmit, every time the panel is developed.
“It's always that trade off. What we're trying to do is go very broad to begin with, with the commercially and clinically most reasonable panel. We then take it to the clinic and then see how much of that the FDA will actually clear because some of these pathogens and especially antimicrobial resistance combinations are still unfortunately very rare. So you may not find enough of them in your trial for the FDA to clear it.”
Currently, OpGen has a current UTI trial underway that started in Q3 2021. There's a guideline by the FDA which requires you to enrol at least 1,500 prospectively enrolled patient samples, with several hundred additional samples enriched with rare pathogens.
“Our goal is to fully enrol that trial here over the summer. It is already CE marked in Europe, but we hope to have a final data readout in the second half of this year and then submit it to the FDA, hopefully by the end of this year.”
Oliver concluded: “UTIs in our view are clearly an underserved area of infectious diseases. They’re of high prevalence and unfortunately increasingly prone to antimicrobial resistance. The better we can diagnose it and quickly, especially in these complicated settings, a more targeted and aggressive drug can be used in the right circumstance, lessening the chance of AR. The easier it will be for physicians then to choose the most appropriate course of antibiotics. In a way it's personalising the choice of antibiotics which is part of precision medicine.
“We're excited to take a what we believe to be a first-in-class and best-in-class product through the clinical trial and through the FDA.”