Drug may lower flu transmission among households, industry trial finds
Baloxavir reduced the rate of laboratory-confirmed influenza in household contacts of flu patients, but the difference in symptomatic flu cases was not significantly better compared to placebo, a phase 3b trial found.
Treatment with a single oral dose of baloxavir may lower transmission of influenza virus to household members compared to placebo, according to an industry-funded study.
To assess whether baloxavir marboxil (baloxavir), which rapidly reduces influenza virus shedding, reduced transmission, researchers conducted a 15-country phase 3b trial assessing the efficacy of single-dose treatment at reducing transmission from index patients to household contacts from October 2019 through April 2024. Influenza-positive index patients ages five to 64 years were randomly assigned 1:1 to receive baloxavir or placebo within 48 hours after symptoms.
The primary end point was transmission of influenza virus from an index patient to a household contact by day 5, as determined by a positive polymerase chain reaction (PCR) test for influenza with a virus type and subtype consistent with those of the index patient. The first secondary end point was transmission of influenza virus that resulted in symptoms. The study was funded by F. Hoffmann–La Roche, which was involved in the design, conduct, and analysis of the trial. Results were published April 23 in the New England Journal of Medicine.
Overall, 1,457 index patients and 2,681 household contacts were enrolled across the 2019 to 2024 influenza seasons. Researchers assigned 726 index patients to baloxavir and 731 to placebo. By day 5, transmission of laboratory-confirmed influenza was significantly lower with baloxavir than with placebo (adjusted incidence, 9.5% vs. 13.4%; adjusted odds ratio [aOR], 0.68 [95.38% CI, 0.50 to 0.93]; P=0.01), for an adjusted relative risk reduction of 29% (95.38% CI, 12% to 45%). The adjusted incidence of transmission of influenza virus that resulted in symptoms was 5.8% with baloxavir and 7.6% with placebo, not a significant difference (aOR, 0.75 [95.38% CI, 0.50 to 1.12]; P=0.16).
The study authors noted that all influenza antiviral drugs exert a selective pressure on viruses, which can result in the emergence of drug-resistant variants. Emergence of drug-resistant viruses during the follow-up period occurred in 7.2% (95% CI, 4.1% to 11.6%) of the index patients in the baloxavir group, and there were no resistant viruses found among household contacts.
Limitations of the study include that most household members were unvaccinated so it remains unclear how previous vaccination may affect transmission after receiving baloxavir.
“Although vaccines will remain the primary control measure for influenza epidemics and pandemics, antiviral drugs play a complementary role, particularly in a pandemic scenario, as well as in persons who are not vaccinated seasonally,” the authors wrote.
An editorial noted that real-world data on baloxavir are lacking, which makes it difficult to determine how the drug would be used in a public health emergency. “During the early phase of an influenza pandemic, when pandemic influenza vaccines are not yet available, early treatment with baloxavir, with its ability to decrease viral shedding, might have greater benefit in reducing transmission than when it is used for seasonal influenza, because most exposed persons will lack specific immunity to the pandemic influenza virus and household transmission is expected to be high,” the editorial stated.