A pill can stop people from developing COVID after being exposed to the virus, trial finds – Image for illustrative purposes only (Image credits: Pexels)
Families sharing a home with someone who has COVID-19 often face an anxious wait to see whether the virus will spread. A five-day course of the oral antiviral ensitrelvir now offers a concrete way to lower that risk for many people. The global Phase 3 SCORPIO-PEP study found that participants who took ensitrelvir after exposure developed symptomatic COVID-19 at a markedly lower rate than those who received placebo. The results, published today in the New England Journal of Medicine, mark the first time any oral antiviral has met its primary goal in a large post-exposure prophylaxis trial.
Clear Reduction in New Infections
In the main analysis of more than 2,000 household contacts who tested negative at the start, 2.9 percent of those given ensitrelvir developed symptomatic COVID-19 by day 10. The figure reached 9.0 percent among participants who received placebo. That difference translates to a 67 percent relative risk reduction. A broader analysis that included everyone who began treatment produced similar results: 4.4 percent versus 10.2 percent. The protective effect appeared quickly and held steady across age groups and regions. No COVID-19-related hospitalizations or deaths occurred in either arm of the study.
Study Design and Timing
Researchers enrolled 2,387 people aged 12 and older across the United States, South America, Africa, and Asia. All participants lived with someone who had recently tested positive for SARS-CoV-2 and begun showing symptoms. Treatment started within 72 hours of the index case’s first symptoms and continued once daily for five days. The trial used a double-blind, placebo-controlled design, so neither participants nor investigators knew who received the active drug. Most people began treatment within 48 hours of the household member’s symptom onset, reflecting real-world exposure scenarios.
Safety and Remaining Questions
Ensitrelvir was generally well tolerated. Adverse events occurred at nearly identical rates in the treatment and placebo groups – 15.1 percent and 15.5 percent, respectively. The most common side effects were mild headache and diarrhea. Some uncertainty remains. The study focused on symptomatic illness rather than all infections, and longer-term follow-up will be needed to understand whether the drug prevents transmission to others or reduces the chance of long COVID. Subgroup data also suggest the benefit may be smaller when treatment begins after infection has already started at a low level.
| Outcome at Day 10 | Ensitrelvir | Placebo |
|---|---|---|
| Symptomatic COVID-19 (primary population) | 2.9% | 9.0% |
| Symptomatic COVID-19 (full population) | 4.4% | 10.2% |
| Serious adverse events | 0.2% | 0.2% |
Next Steps for Availability
Shionogi has already begun a rolling submission to the U.S. Food and Drug Administration for ensitrelvir as post-exposure prophylaxis. If approved, the pill would give households and high-risk contacts a simple oral option they can start at home. Health authorities will still weigh how the drug fits alongside vaccination, masking, and testing. For now, the trial provides the clearest evidence yet that a short course of an oral antiviral can meaningfully interrupt household spread of COVID-19.