Single Dose of Xofluza Reduces Odds of Untreated Household Members Contracting Influenza

Key Takeaways

Baloxavir marboxil reduced influenza transmission by 32% among untreated household members, with a 29% reduction in laboratory-confirmed cases by day 5.
The antiviral works by inhibiting the cap-dependent endonuclease protein, reducing viral replication and disease duration.
The CENTERSTONE trial showed no significant reduction in symptomatic transmission, but no new safety signals were identified.
This trial is the first to demonstrate an antiviral effect in reducing influenza transmission within households, highlighting its potential public health impact.

Reductions of about 32% were observed during the study.

A single oral dose of baloxavir marboxil (Xofluza; Genentech, Roche) taken by patients with influenza reduced the odds of untreated household members contracting the virus by approximately 32%, according to research findings published in The New England Journal of Medicine. Additionally, baloxavir marboxil demonstrated a clinically meaningful reduction of influenza virus transmission with symptoms; however, statistical significance was not reached.^1,2

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About the Trial

Trial Name: Study to Assess the Efficacy of Baloxavir Marboxil Versus Placebo to Reduce Onward Transmission of Influenza A or B in Households

ClinicalTrials.gov ID: NCT03969212

Sponsor: Hoffmann-La Roche

Completion Date: May 10, 2024

Baloxavir marboxil is a first-in-class, single-dose medicine administered orally with an innovative mechanism of action designed to block viral replication through the inhibition of the cap-dependent endonuclease protein, reducing the duration of disease and its infectiousness. It is approved in over 75 countries for the treatment of uncomplicated influenza types A and B, and in several countries, it is approved for the treatment of influenza in otherwise healthy patients and as post-exposure prophylaxis. This treatment represents the first innovation in mechanism of action for an influenza antiviral for children, adolescents, and adults that has been approved in nearly 20 years, according to a news release from Roche.¹

The results, published in The New England Journal of Medicine,are from the CENTERSTONE trial (NCT03969212), a multicenter, randomized, double-blind, placebo-controlled phase 3b clinical efficacy study.^2,3 Prior to this study, baloxavir marboxil was observed to rapidly reduce influenza virus shedding, suggesting it may reduce transmission of the virus. Previous studies have shown that treatment with neuraminidase inhibitors has not presented sufficient evidence that they prevent transmission to contacts.^2,3

A total of 1457 otherwise healthy index patients were randomly assigned to receive either baloxavir marboxil (n = 726) or placebo (n = 731) if the onset of their influenza-related symptoms was within 48 hours of screening. Patients under the age of 12 received 2 mg/kg of baloxavir marboxil if they weighed less than 20 kg or 40 mg if 20 kg or more. Patients 12 years or older received 40 mg if weighing less than 80 kg and 80 mg if 80 kg or more. Additionally, 2681 household contacts were enrolled.^2,3

The findings demonstrated that by day 5, the transmission of laboratory-confirmed influenza was noticeably lower with baloxavir marboxil (adjusted incidence: 9.5%) compared with placebo (adjusted incidence: 13.4%; adjusted odds ratio, 0.68 [95.38% CI, 0.50–0.93]; P = .01), with an adjusted relative risk reduction of approximately 29% (95.38% CI [12–45]). Additionally, the adjusted incidence of transmission of the influenza virus by day 5 that resulted in symptoms was about 5.8% in those treated with baloxavir marboxil and 7.6% with placebo. Despite this difference, it was not considered significant (adjusted odds ratio: 0.75 [95.38% CI 0.50–1.12]; P = .16), according to the authors.²

Further, the emergence of drug-resistant viruses during the follow-up period occurred in about 7.2% (95% CI 4.1–11.6) of the index patients in the baloxavir marboxil group. There were no resistant viruses detected in household contacts, and no new safety signals were identified throughout the study’s duration.²

“This trial is the first to demonstrate an antiviral effect that reduces transmission of influenza viruses within a household. This result may potentially have broad-reaching implications for public health,” Levi Garraway, MD, PhD, chief medical officer and head of global product development at Roche, said in a news release. “This publication reminds us of the ongoing societal need for solutions that can help ease the burden of influenza on society.”¹

REFERENCES

1. Roche. New England Journal of Medicine publishes phase III data showing single-dose Xofluza significantly reduces influenza virus transmission. News release. April 24, 2025. Accessed April 30, 2025. https://www.roche.com/media/releases/med-cor-2025-04-25

2. Monto AS, Kuhlbusch K, Bernasconi C, et al. Efficacy of Baloxavir Treatment in Preventing Transmission of Influenza. New Engl J Med. 2025;392(16):1582-1593. doi:10.1056/NEJMoa2413156

3. Study to Assess the Efficacy of Baloxavir Marboxil Versus Placebo to Reduce Onward Transmission of Influenza A or B in Households. ClinicalTrials.gov identifier: NCT03969212. Updated April 24, 2025. Accessed April 30, 2025. https://clinicaltrials.gov/study/NCT03969212