New Roche flu drug can drive resistance in influenza viruses: researchers

[November 26, 2019]  By Julie Steenhuysen

CHICAGO (Reuters) - Roche's influenza treatment Xofluza, a one-dose pill that can clear flu symptoms within days, may cause a mutation of the virus that leads to drug resistance, researchers reported on Monday.

Results of their study suggest that common flu strains can quickly acquire resistance to the drug. They caution patients who receive it - especially children - should be watched for drug resistance.

The antiviral won U.S. approval last year to treat people 12 and older, and earlier this month was approved for patients at high risk of flu complications.

The Swiss drugmaker is seeking to establish Xofluza, which has a list price of $150, as a more convenient alternative to its older Tamiflu, which is taken twice daily for five days and is facing competition from cheaper generics.

The study published on Monday in Nature Microbiology by researchers at the University of Wisconsin-Madison involved flu samples from an 11-year old boy in Japan diagnosed with the flu last January and treated with the drug, known chemically as baloxavir.

Although he improved initially, the boy's fever returned, and two days later, his 3-year-old sister was diagnosed with the flu.

The Wisconsin team, led by flu expert Yoshihiro Kawaoka, sequenced DNA of flu samples from the siblings and found the girl's virus harbored a single mutation resistant to baloxavir.

"It tells you the virus acquired resistance during treatment and transmitted from brother to sister," Kawaoka said in a statement.

Baloxavir was first licensed in Japan, where developer Shionogi & Co retains marketing rights and has 40% of the antiviral market there.

Kawaoka said prior studies had also found drug resistance, which led him to study resistance in larger groups of patients exposed to H1N1 or H3N2, two common flu strains.

For H1N1, the team tested 74 samples from infected patients before treatment and 22 samples from patients both before and after treatment. They found no mutations in any of the samples before treatment, but 23% of patients carried drug-resistant mutations after treatment.

Tests of H3N2 samples from 40 adults and 101 children found two of the children possessed the mutation. They also studied 16 samples before and after treatment from four adults and 12 children, finding no mutations in adult samples but four in the samples from children.

The team then grew the mutated viruses in the lab and found they were easily transmitted from infected to healthy animals.

Although it is unlikely baloxavir will cause widespread resistance, Kawaoka said it could be a problem when infected patients are in close proximity.

Patients with H1N1 or H3N2 who develop resistance to baloxavir treatment do respond to other virus-fighting drugs, he said.

(Reporting by Julie Steenhuysen; Editing by Bill Berkrot)

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