New study published in NEJM finds antiviral ensitrelvir significantly reduces COVID-19 infection risk among household contacts of infected patients. Learn more.
Antiviral ensitrelvir has shown significant promise in preventing the spread of COVID-19 within households, according to a recent Phase III randomized controlled trial published in the New England Journal of Medicine (NEJM). The study found that post-exposure prophylaxis with ensitrelvir reduced the infection rate by 67% among household contacts compared to those receiving placebo.
The research involved over 200 index patients who were exposed to SARS-CoV-2 and their respective household contacts. Household contacts were randomly assigned to receive either ensitrelvir or a placebo. The study followed these participants for up to 14 days, monitoring the incidence of COVID-19 infection.
Key findings from the trial include:
Over 98% of household contacts tested positive for SARS-CoV-2 antibodies, indicating previous exposure. Antiviral therapy was initiated in approximately 18.7% of index patients. The overall infection rate among ensitrelvir recipients was significantly lower than that of placebo recipients (2.9% vs. 9.0%, risk ratio = 0.33). Similar adverse event rates were observed between the two groups, with no significant differences noted in serious adverse events.
The study also revealed several important subgroups where ensitrelvir demonstrated effectiveness:
In a subgroup analysis of household contacts at higher risk for severe disease (older adults and those with pre-existing conditions), the infection rate was 2.4% in the ensitrelvir group compared to 9.9% in the placebo group. The post-exposure prophylaxis regimen also showed a 34% relative risk reduction in SARS-CoV-2 transmission within households.
The authors emphasized that households are critical sites for SARS-CoV-2 transmission, with secondary attack rates as high as 32 to 48% during the omicron era. Nonpharmaceutical interventions such as masking and isolation can lower this risk but may not be fully protective in all settings.
Ensitrelvir's efficacy was consistent across various subgroups, including older adults and those at higher risk for severe disease. The researchers ensitrelvir recipients had lower viral loads and symptom scores compared to placebo group participants during their illness.
Aeron Hurt, Ph.D., vice president of global medical science at Shionogi, highlighted the potential public health benefits of ensitrelvir: "By preventing COVID-19, people can avoid not only potentially serious consequences of acute disease but also the risk of exacerbating pre-existing conditions or acquiring new conditions such as long COVID."
The findings suggest that ensitrelvir could be a valuable tool for reducing household transmission during outbreaks in congregate living environments. Further research is needed to explore its effectiveness in other unprotected contexts.
Publication details: Frederick G. Hayden et al, "Ensitrelvir for Covid-19 Postexposure Prophylaxis in Household Contacts," New England Journal of Medicine (2026).
This study underscores the importance of post-exposure prophylaxis as a strategy to mitigate SARS-CoV-2 transmission within households and highlights ensitrelvir's potential role in public health strategies against COVID-19.
