Single-dose baloxavir reduces household transmission of influenza

A single dose of baloxavir given to an index patient (IP) reduces the odds of influenza transmission to untreated household contacts (HHCs) by 32 percent vs placebo, according to the results of the phase IIIb CENTERSTONE trial.

Single‐dose baloxavir marboxil is a selective influenza cap‐dependent endonuclease inhibitor, which shows potent antiviral activity in treating both otherwise healthy and high‐risk adults, as well as paediatric influenza patients. [Influenza Other Respir Viruses 2024;18:e13302] As baloxavir rapidly reduces influenza virus shedding, it may reduce viral transmission. An international team of researchers, including Professor Benjamin Cowling of the School of Public Health, University of Hong Kong, set up a double-blind, randomized, placebo-controlled, global trial to test this hypothesis.

The study enrolled 1,457 influenza-positive IPs (age range, 5–64 years) and 2,681 HHCs across the 2019–2024 influenza seasons. A total of 726 IPs were assigned to receive baloxavir within 48 hours of symptom onset and 731 to placebo. The primary endpoint was laboratory-confirmed transmission of influenza virus from an IP to an HCC by day 5, following the incubation period of 1–4 days. [N Engl J Med 2025;392:1582-1593]

The primary endpoint was met. By day 5, transmission of laboratory-confirmed influenza was significantly lower with baloxavir vs placebo (adjusted incidence, 9.5 vs 13.4 percent; adjusted odds ratio, 0.68; 95.38 percent confidence interval [CI], 0.50–0.93; p=0.01). The adjusted relative risk reduction was 29 percent. “A consistent directional transmission benefit was observed with baloxavir across all subgroups, including influenza virus type/subtype [A(H1N1)pdm09, A(H3N2), B], influenza season, region [Asia/not Asia], and IP’s age [<12, ≥12–≤30, >30 years],” added the researchers.

The first secondary endpoint was transmission of influenza virus by day 5 that resulted in symptoms, defined as the proportion of HHCs meeting the primary endpoint and either: temperature ≥38.0°C plus one respiratory symptom, or one respiratory symptom plus one general systemic symptom, with or without fever (in HHCs aged ≥12 years); or temperature ≥38.0°C plus signs or symptoms of an upper respiratory tract infection (in HHCs aged <12 years). The adjusted incidence of transmission of influenza virus by day 5 that resulted in symptoms was 5.8 percent with baloxavir and 7.6 percent with placebo. “Baloxavir showed a clinically meaningful reduction in transmission of influenza virus resulting in symptoms, but statistical significance was not reached [adjusted odds ratio, 0.75; 95.38 percent CI, 0.50–1.12; p=0.16],” noted the researchers.

Baloxavir led to a faster reduction in viral titres, with a mean reduction of 2.22 log₁₀ TCID₅₀/mL by day 3 compared with 1.85 log₁₀ TCID₅₀/mL for placebo. Emergence of drug-resistant viruses during the follow-up period occurred in 7.2 percent of IPs in the baloxavir group, but there was no evidence of transmission of resistant viruses to HHCs. Baloxavir was well tolerated with no new safety signals identified.

“These results highlight baloxavir’s potential not only to treat influenza, but also to reduce its spread within communities,” said Cowling. “This dual effect could transform how we manage seasonal influenza and prepare for future pandemics.”