Stephen I. Feller , 2025-04-24 21:10:00
April 24, 2025
3 min read
Key takeaways:
- A single oral dose of baloxavir reduced household transmission of influenza in a phase 3b trial.
- The drug may be best fit for use early in an influenza pandemic, researchers and experts said.
A trial of the influenza antiviral baloxavir suggests that the drug could be used as post-exposure prophylaxis to prevent infection among household contacts of someone infected with the virus.
“We have been trying to see if treatment resulted in protection of contacts for years with oseltamivir and Relenza,” Arnold S. Monto, MD, co-director of the Michigan Center for Respiratory Virus Research and Response at the University of Michigan, told Healio.
“Seeing that baloxavir reduced virus shedding when used in treatment much faster than oseltamivir was the inspiration for the trial,” he said.
Baloxavir was FDA approved in 2018 for the treatment of acute, uncomplicated influenza in people aged 12 years and older who seek treatment within 48 hours of symptom onset. Since 2020, the drug has been approved as post-exposure prophylaxis (PEP) for people aged at least 12 years who have had contact with an infected person.
According to Monto and colleagues, however, trial results of baloxavir, as well as other antivirals, to reduce influenza transmission “have not been conclusive.”
The researchers conducted a multicountry, phase 3b trial of a single oral dose of baloxavir to reduce household transmission of influenza, assigning 1,457 index patients and 2,681 household contacts 1:1 to receive the drug or a placebo 48 hours after symptom onset across the 2019 through 2024 influenza seasons.
Influenza-positive patients ranged from age 5 years to 64 years, with 726 given baloxavir and 731 given a placebo. Of the household contacts, 1,345 were treated with baloxavir and 1,336 were given a placebo. Most household contacts were also unvaccinated, the researchers reported.
According to the study, by day 5, transmission of lab-confirmed influenza was “significantly” lower among participants given baloxavir than those who received a placebo with an adjusted incidence of 9.5% vs. 13.4% and an adjusted odds ratio of 0.68 (95.38% CI, 0.5-0.93).
The adjusted incidence of transmission by day 5 that resulted in symptoms was 5.8% with baloxavir and 7.6% with placebo, with an adjusted odds ratio of 0.75 (95.38% CI, 0.5-1.12), which the researchers said was not significant.
Additionally, drug-resistant influenza strains were seen in 7.2% (95% CI, 4.1%-11.6%) of study participants who received baloxavir and resistant strains were not seen in any household contacts, according to the study.
Although Monto and colleagues found that household transmission of influenza was lower in the baloxavir group than in the placebo group, they note that symptomatic infections did not decrease significantly. They also said that lower incidence of infection in the placebo group could potentially be blamed on COVID-19 pandemic-related changes in behavior.
In an accompanying commentary, Timothy M. Uyeki, MD, MPH, chief medical officer in the CDC’s Influenza Division, and colleagues wrote that antiviral treatment for people with influenza is recommended as soon as possible and is generally most effective if started within 48 hours of symptom onset, and that there may be benefit from using baloxavir as PEP.
They said, however, that “the best way to prevent seasonal influenza is through annual influenza vaccination” with antiviral medications used as an adjunct to vaccines.
“Challenges and questions remain about how to use antiviral medications most effectively because of the short incubation period and short serial interval for influenza,” Uyeki and colleagues wrote. “This includes how to operationalize early diagnosis and antiviral treatment to achieve the greatest benefit, especially for persons at increased risk for complications and those living in households with such persons.”
They note that there is a lack of data on efficacy, effectiveness and dosing of baloxavir for either treatment or PEP, adding that the drug may be best used during the early phase of an influenza pandemic, before pandemic influenza vaccines are available, both for treatment and to prevent transmission.
In speaking with Healio, Monto also said that since the influenza vaccine is not 100% effective at preventing infection — and in some years is “especially” less effective — baloxavir as PEP could be an important tool in the case of a pandemic, especially for people with risk factors for severe disease.
“The results indicate that there is reduction of transmission, but it is not total,” Monto said. “The takeaway is that there is now an added reason to use the drug for treatment of influenza. Again, it doesn’t replace the vaccine. And it may be all we have at the start of a pandemic.”
References:
Perspective
Having a means to decrease influenza transmission in households would be valuable and lessen the disruptive effects of the virus. The positive findings of the study by Monto and colleagues provide a basis for better management of influenza cases.
However, the absolute risk reduction is about 4%, so the number needed to treat is relatively high to prevent one transmission event. Nevertheless, this is an important proof of concept and the lack of drug-resistant transmission is reassuring.
Amesh A. Adalja, MD
Senior Scholar, Johns Hopkins Center for Health Security
Disclosures: Adalja reports that he has consulted for Shionogi on COVID-19-related pharmaceuticals.
Sources/Disclosures
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Disclosures:
Monto reports participation in an end point review committee for Hoffmann-La Roche Limited. Please see the study for all other authors’ relevant financial disclosures. The editorial authors report no relevant financial disclosures.
