Baloxavir—the active form of the antiviral Xofluza—is better than Tamiflu (oseltamivir phosphate) at treating mice infected with influenza A H5N1 virus, commonly known as bird flu. The finding suggests that Xofluza, which is approved by the US Food and Drug Administration, should be considered as a treatment alongside Tamiflu, says Richard J. Webby, an influenza expert at St. Jude Children’s Research Hospital, who led the study (Nat. Microbiol. 2025, DOI: 10.1038/s41564-025-01961-5).
“I am not a clinician, so am in no real position to suggest treatment options,” Webby says in an email. “But if I was infected with an H5N1 virus, I would be asking for both drugs.”
In the study, mice were given cow’s milk infected with H5N1 virus via one of three routes: mouth, nose, or eyes. Survival rates of mice treated with baloxavir alone were as high as 25% for those infected orally, 75% for those infected nasally, and 100% for those infected ocularly, compared with 25%, 40%, and 63% for mice treated with Tamiflu. Infected mice that did not receive treatment died.
Webby cautions that H5N1 infection is highly lethal in mice but often mild and limited to eye infections in humans—at least that’s what’s been observed in the US so far. “The mouse model would have to be considered the very worst-case scenario,” he says.
Megan L. Shaw, who studies infectious diseases at the University of the Western Cape and was not involved in the research, says that this study is significant because it’s the first to show that baloxavir is better than oseltamivir for battling H5N1 infections. “It also demonstrates the critical importance of testing antiviral drugs in animal models, as these results could not have been predicted by conducting studies in in vitro cell models,” she says in an email.
Andrew Mehle, who studies influenza at the University of Wisconsin–Madison and was also not involved in the research, says the results could guide doctors considering treatment options and influence agencies that stockpile drugs.
Both Mehle and Shaw point out that previous research has shown that influenza viruses can develop resistance to Xofluza. “Combination therapy where Xofluza is paired with a different class of antiviral drug may offer an even better treatment plan while dramatically reducing the ability of the virus to escape drug pressures,” Mehle says in an email.
Mehle also notes that the US government funded the initial research behind Xofluza’s target in the 1970s and ’80s. “The ability of Xofluza to inhibit a brand-new virus strain that threatens the human population is the perfect example of how fundamental research programs have boosted our pandemic preparedness,” he says.