A groundbreaking international clinical trial has demonstrated that the antiviral drug ensitrelvir can significantly reduce the risk of COVID-19 infection among household contacts of infected individuals. The study, co-designed by University of Virginia School of Medicine professor Dr. Frederick G. Hayden, marks the first successful trial of an oral antiviral for COVID-19 prevention.
The SCORPIO-PEP trial enrolled more than 2,000 participants who had been exposed to COVID-19 within their households. Participants received either ensitrelvir or a placebo within 72 hours of their household member developing symptoms, with the requirement that they themselves tested negative for SARS-CoV-2 and were asymptomatic at enrollment.
"Overall, it was highly effective for protecting the household contacts from developing COVID during that 10-day period," said Dr. Hayden, who presented the findings at the Conference on Retroviruses and Opportunistic Infections in San Francisco.
Significant Reduction in Infection Risk
The double-blinded trial, conducted between June 2023 and September 2024, showed compelling results. Among participants who received a placebo, 9% developed confirmed COVID-19, compared to just 2.9% of those who received a five-day course of ensitrelvir—representing a 67% reduction in infection risk.
The drug's protective effect was even more pronounced among vulnerable populations. Approximately 37% of trial participants had at least one risk factor for developing serious complications from COVID-19, and in this high-risk group, ensitrelvir reduced infection risk by 76%.
"In addition to vaccination, post-exposure prophylaxis with timely use of an oral antiviral would be a valuable way to help prevent COVID-19 illness in people who have been exposed, especially people at high risk for severe disease," Dr. Hayden explained.
Safety Profile and Current Status
Researchers reported that ensitrelvir was generally well-tolerated, with no increase in adverse effects compared to the placebo group. Importantly, no hospitalizations or deaths occurred in either the treatment or placebo arms of the study.
Ensitrelvir is already approved and being used in Japan for the treatment of mild to moderate COVID-19 cases. However, before it can be utilized as a preventive medication in the United States, the Food and Drug Administration would need to grant approval for this specific indication.
"This is the first clinical trial of an oral antiviral drug to show significant protection against COVID-19," noted Dr. Hayden. "If approved by the Food and Drug Administration for this purpose, it would be an important addition to current preventive strategies."
Potential Impact on Vulnerable Populations
The findings suggest that ensitrelvir could become a valuable tool for protecting high-risk individuals who have been exposed to the virus, potentially filling an important gap in the current arsenal of COVID-19 prevention strategies.
"I'm hoping that in the future, this would be a possibility for protecting individuals, in particular those with risk conditions, if they had an exposure to SARS-CoV-2," Dr. Hayden said.
As COVID-19 continues to circulate globally, having effective post-exposure prophylaxis options could be particularly beneficial for immunocompromised individuals, elderly populations, and those with underlying health conditions who remain at elevated risk for severe outcomes despite vaccination.
