As health agencies and drugmakers struggle to deliver enough vaccine to curb the H1N1 pandemic, the World Health Organization (Geneva) has identified more than three dozen cases of resistance to Tamiflu. It's a small percentage compared with the hundreds of thousands of people who have actually been sickened with this new flu, but it's key to monitor because resistance to antivirals can signal a virus mutation, prompting a change in both antivirals and vaccines.
Translational Genomics Research Institute (TGen; Phoenix) has just submitted a request to the FDA for emergency use authorization (EUA) of a new test, called Flu-MAMA (Mismatched Amplification Mutation Assay), to diagnose the H1N1 flu virus. But in the bigger picture, it's also designed to identify resistance to Tamiflu, the primary antiviral drug on the market to treat H1N1.
"TGen tools look very closely at these viruses and monitor if a strain is resistant, but also if there is a background level of resistance. This is very important for drug studies so you know if drugs are working or if resistance is creeping up," David Engelthaler, director of programs and operations for TGen North (Flagstaff, Arizona), the company's Pathogen Genomics Division, told Medical Device Daily. "One thing we know for sure is that it will mutate. All flu viruses change. When you see resistance developing, it is mutating. We want to identify those cases to prevent further spread of the flu."
Engelthaler said it would be the only resistance test available that uses a standard molecular technique that rapidly makes exact copies of specific components of H1N1's genetic material.
Tgen's test is actually a series of three real-time PCR tests to diagnose the flu, identify the strain and then to determine if it is resistant to Tamiflu.
Tgen's submission to the FDA includes data on how its H1N1 assay works in comparison to CDC PCR tests.
The influenza A detection portion of the assay, when compared to the CDC assay, has 96% positive agreement and 100% negative agreement; the H1N1 portion has 95.5% positive agreement with the CDC assay and 100% negative agreement.
Until recently, the CDC's PCR-based tests were the only authorized way to diagnose the disease. Gen-Probe (San Diego) received EUA for its Prodesse ProFlu-ST test to diagnose the flu earlier this week, although it doesn't have the capacity to test for antiviral resistance that comes with the Flu-MAMA (MDD, Nov. 3, 2009).
Because Tgen's test can identify H1N1, it is also being used to aid in drug development.
"When swine first popped up it appeared that Tamiflu worked in most cases, but over the past couple of months, some individual cases are resistant," Engelthaler said. "We're hoping if this gets FDA approval, it will have an impact on diagnostics and surveillance, allowing for state labs to do their own resistance testing rather than just sending samples to the CDC."
The assay is "very effective" with strains in the U.S., and it's expected to have the same accuracy with strains around the world, said Engelthaler, who is the former state epidemiologist for Arizona and former State of Arizona Biodefense Coordinator.
TGen is working with Adamas Pharmaceuticals (Emeryville, California), which is developing a triple-drug combination to treat influenza and to impede resistance.
"Tgen's diagnostic test has been a useful tool in our research and is an important contribution to the influenza field," said Gregory Went, PhD, CEO and chairman of Adamas.
The test was developed in collaboration with PathoGene (Flagstaff, Arizona), a company recently formed as a partnership between TGen and Technical Resource Management, a private firm that runs CLIA-certified labs.
Lynn Yoffee, 770-361-4789;