NEW YORK ─ Avisa Diagnostics is developing 10-minute breath tests to detect metabolized urease bacteria in patients with ventilator-associated pneumonia and post-COVID-19 respiratory infections.
The Santa Fe, New Mexico-based company, formerly known as Avisa Pharma, believes its point-of-care drug-device platform can help guide physicians to quickly alter treatments, prevent the overuse of broad-spectrum antibiotics, and provide vital information to prevent serious respiratory infections, its president and CEO, David Joseph, said in an interview.
Avisa's technology involves administering a tracer drug, 13C-urea, to the lungs where it is metabolized and converted to 13CO2 generated by urease-containing bacteria.
A patient taking the Avisa BreathTest provides a baseline sample and then uses a nebulizer to deliver the drug. The platform uses a laser spectrometer to detect and measure the presence of urease pathogens by evaluating the wavelengths of signals produced by exhaled carbon dioxide with the 13-isotope. The system calculates differences in signals produced during baseline testing and those produced after the tracer drug has been metabolized, and provides measurements of bacterial load for targeted indications, Joseph said.
Avisa is preparing an Investigational Device Exemption application to the US Food and Drug Administration that, if successful, will enable it to participate in a pivotal study to evaluate its breath test in patients with ventilator-associated pneumonia or post-COVID-19 long-haul respiratory infections.
The studies, planned to start during the first quarter of 2022, will enroll patients in up to 30 clinical sites to evaluate the clinical utility of the breath test in advance of an application to the FDA for premarket approval. Avisa recently hired Barbara Bunger, previously a global director of clinical research and corporate clinical development at Becton Dickinson, as its vice president of clinical development responsible for designing and executing a clinical development plan to obtain the US regulatory approval.
"We're looking at bacterial infections of the worst kind that would have you hospitalized on the most powerful broad-spectrum antibiotics, so the overall role of the drug-device platform is to help mitigate overuse of these antibiotics, prevent infection, and monitor therapies," Joseph said.
In May, Avisa began trading on the Canadian Securities Exchange. The public listing enables it to use up to $41 million over three years from a share subscription and drawdown agreement with Gem Global.
On Monday, the firm announced that it intends to conduct a private placement of 1,390,000 common shares to raise approximately C$375,000 ($298,839) at a price of C$.27 per common share. Avisa said it intends to use the net proceeds from the offering for operations and expansion of its business and for general working capital purposes.
The company believes its first in vitro diagnostic test will hit the market in early 2024, Joseph said.
Since 2010, when the firm was launched after licensing technology for its tests from the University of New Mexico, Avisa has been investing in product and clinical development, Joseph said. The firm has developed a ready-for-manufacturing spectrometer and completed clinical proof-of-concept studies for its drug-device platform in cystic fibrosis, tuberculosis, and community-acquired pneumonia.
The cystic fibrosis study by researchers at the University of New Mexico showed that isotope ratios in CF patients with Pseudomonas aeruginosa may be higher than in control patients 10 minutes after the inhalation of 13C-urea. Joseph said that the sensitivity of the platform in the CF study was almost 100 percent and added that based on its current performance, Avisa expects the platform to demonstrate sensitivity and specificity levels in future clinical studies of between 90 and 95 percent.
The point-of-care breath tests have the potential to enable clinicians to intervene early with appropriate treatments and prevent full-blown infections that can be fatal, partly because clinicians using its tests will not have to wait hours and sometimes days to obtain laboratory results, he said.
Combined, Joseph added, the US testing markets for ventilator-associated pneumonia and post-COVID-19 long-haul respiratory infections is greater than $3.3 billion.
Many of patients with SARS-CoV-2 who require admission to an intensive care unit for invasive ventilation are at significant risk of developing ventilator-associated pneumonia. Before the onset of the pandemic, 1.7 million people in the US each year used mechanical ventilators, and about 400,000 contracted ventilator-associated pneumonia involving mortality rates between 30 and 50 percent, Joseph noted.
Though ventilator-associated infections and post-COVID-19 long-haul respiratory infections are a priority, Avisa is also developing an assay to monitor patients with chronic obstructive pulmonary disease and to help prevent exacerbation or worsening of the condition, and it is investigating the potential of using its platform to detect and monitor cystic fibrosis exacerbations and C. diff infections. The firm believes its breath tests could also be used to rule out urease-containing pathogens such as S. aureus, P. aeruginosa, Klebsiella, and H. influenzae that make up 15 percent of infections in the emergency department. The main pathogen detected in post-COVID long-haul patients will probably be P. aeruginosa, which causes airway infections in non-cystic fibrosis bronchiectasis, Joseph said.
Emerging breath-based technologies
Many developers are exploring different detection technologies for breath testing for a number of indications.
"The emergence of the COVID-19 pandemic has only served to reinforce a trend that had been gaining momentum for some time, that better and novel diagnostic solutions are needed in order to identify disease early and to help direct effective therapies," Chris Claxton, VP of investor relations and marketing at Cambridge, UK-based Owlstone Medical, said in an interview. "Metabolic markers have long been measured in urine and blood for a range of diseases. Many metabolites are volatile at body temperature, and so, breath represents a rich and completely noninvasive way to collect and measure them. While the space is relatively young aside from a handful of applications, on this basis it has the potential to completely transform the future of diagnostic testing."
Owlstone Medical is preparing to launch breath-based testing for digestive health in its UK laboratory, using gas chromatography to detect hydrogen and methane biomarkers for the diagnosis of gastrointestinal conditions such as small intestine bacterial overgrowth, or SIBO, and food intolerance.
Singapore's Health Sciences Authority recently approved on a provisional basis a volatile organic compound breath test developed by Breathonix to rapidly detect COVID-19, and Cambridge, UK-based Rapid Biosensor Systems is targeting a clinical need for more rapid and affordable tuberculosis screening by combining breath sampling with evanescent-wave optical sensing.
Avisa intends to initially target its tests for use by pulmonologists, emergency room doctors, and critical care and infectious disease physicians, who are working in hospitals and urgent care clinics, Joseph said.
Using internal sales staff, the firm plans to sell a kit that includes the tracer drug, mouthpiece, and nebulizer for use with its portable spectrometer.
Avisa's future customers will have an option to obtain the spectrometer for free and pay for a minimum number of tests per month, Joseph said. For outpatient testing, the cost will amount to about $200 each for 40 tests, he said.
The firm will seek CPT codes that enable reimbursements for its tests, Joseph said, adding that a test that uses 13C-urea to detect H. pylori infections, launched by Exalenz Bioscience, is already being reimbursed by payors — a development that may bode well for the reimbursement of Avisa's tests.
Conditions targeted by the Avisa breath test have high prevalence globally. The company has future plans to obtain CE marking that would enable the sale of its tests in the European Union and other regions that accept the designation, and the firm intends to obtain regulatory approval to market its tests in China and Japan, Joseph said.