CDC Mounts Multifaceted Response to New Flu Antiviral Approval

By Brenda L. Mooney, /alert Contributor
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A new influenza antiviral drug gives clinicians another valuable weapon to combat flu illness, according to the CDC, which pointed out that baloxavir marboxil has benefits similar to other approved flu antiviral drug but works differently.

Public health officials also suggested that the new drug could be especially helpful in the event of the emergence of widespread resistance to the other influenza antiviral drugs, i.e. oseltamivir, zanamivir and peramivir.


Woman with the flu. Source: Getty

As part of its response to FDA approval of the drug, CDC took a number of steps, including developing a new assay to test for markers of baloxavir resistance.

Baloxavir is a cap-dependent endonuclease (CEN) inhibitor that interferes with viral RNA transcription and blocks virus replication. On its website, the CDC explained that the new drug blocks the ability of the virus to make copies of itself within an infected cell. The other available flu antiviral medications are “neuraminidase inhibitors,” which do not directly interrupt replication within an infected cell but instead work to prevent new copies of the virus from leaving the infected cell and spreading to healthy cells, the article noted.

In response to the FDA approval, CDC conducted next-generation sequencing (NGS) and analyzed thousands of influenza viruses.

At the same time, a laboratory assay using pyrosequencing technology was developed to detect the principal markers of baloxavir resistance in clinical specimens. The “PA-38T/M/F” markers were most commonly detected in viruses collected from baloxavir-treated patients.

Laboratory assays also were developed to test the susceptibility of influenza viruses to baloxavir in cell cultures. While the “one-cycle infection-based” assay measures how well baloxavir inhibited the early stages of influenza virus infection at a single cell level, the “multi-cycle infection-based” assay measured how well baloxavir blocked infection of neighboring healthy cells.

The difference, according to CDC authors, is that the multi-cycle assay is primarily used to test highly pathogenic avian influenza (HPAI) viruses with pandemic potential vs. the one-cycle assay, which mainly is used for testing of seasonal and other influenza viruses.

CDC also has created a summary for clinicians on baloxavir as part of its public and clinician education and outreach activities materials.

“Antiviral resistance and reduced susceptibility to the neuraminidase inhibitors and to baloxavir among circulating influenza viruses is currently low, but this can change,” public health officials advised. “Antiviral resistance and reduced susceptibility can occur sporadically, or emerge during or after antiviral treatment in some patients (e.g., immunocompromised). Following treatment with baloxavir, emergence of viruses with molecular markers associated with reduced susceptibility to baloxavir has been observed in clinical trials.”