At this week’s CROI conference, Japan-based Shionogi presented results for its investigational antiviral, ensitrelvir, that demonstrated a 67% reduction in the risk of developing COVID-19 in uninfected individuals treated after exposure, compared to a placebo at day 10.1 Of the study participants treated with ensitrelvir, 2.9% developed symptomatic COVID-19 compared to 9.0% of participants on placebo (risk ratio: 0.33; 95% CI: 0.22-0.49; p<0.0001) at Day 10, the primary endpoint.2
This study shows the potential for a post-exposure prophylaxis (PEP) therapy, especially as there are no FDA-approved treatments in this category.
“COVID-19 remains a major threat to public health, and the best way to avoid the serious and long-term complications associated with the virus is to reduce the risk of being infected in the first place,” Frederick Hayden, MD, Professor Emeritus of Clinical Virology and Professor Emeritus of Medicine, University of Virginia School of Medicine, said in a statement. “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.”2
Study Specifics
The results are from the SCORPIO-PEP trial, which is a global study that included 2,387 participants aged 12 years and older across the US and several countries in South America, Africa, and Asia. Study participants with a negative screening test for SARS-CoV-2 infection and no symptoms, who were exposed to a person living in their household with symptomatic COVID-19, were randomly assigned in a 1:1 ratio to receive ensitrelvir (125 mg) or placebo once daily. Study participants began treatment within 3 days of when the household member with COVID-19 began showing symptoms. Participants then continued ensitrelvir or placebo for 5 days.2
What You Need to Know
The investigational antiviral reduced the risk of developing symptomatic COVID-19 by 67% in uninfected individuals exposed to the virus, compared to a placebo.
Ensitrelvir is the first oral antiviral to demonstrate COVID-19 prevention in a clinical trial, addressing a major unmet need, as there are currently no FDA-approved PEP treatments for COVID-19.
Ensitrelvir has received full approval in Japan, emergency approval in Singapore, and FDA Fast Track designation, with trial results showing it was well tolerated with no COVID-19-related hospitalizations or deaths.
Overall, ensitrelvir was generally well tolerated, with similar rates of adverse events in the ensitrelvir group and the placebo group (15.1% and 15.5%, respectively).2 There were no COVID-19 related hospitalizations or deaths.2
Ensitrelvir is an investigational antiviral that suppresses the replication of SARS-CoV-2 by selectively inhibiting the viral 3CL protease. Ensitrelvir was granted Fast Track designation by the FDA last year for COVID-19 treatment. In Japan, ensitrelvir, known as Xocova, received emergency regulatory approval in 2022 and full approval in March 2024 for the treatment of COVID-19. Ensitrelvir was also made available in Singapore based on the Special Access Route application in 2023. It remains an investigational drug outside of Japan and Singapore.3
“SARS-CoV-2 continues to circulate and there are still thousands of hospitalizations and hundreds of COVID-19 deaths each week,” Simon Portsmouth, MD, FRCP, senior vice president, head of Clinical Development, said in a statement. “If we can reduce the risk of infection among individuals who are exposed to SARS-CoV-2, this fulfills an important unmet medical need. Oral antivirals have changed the way we treat and prevent other infectious diseases, including influenza and HIV, and there is an opportunity to do the same with COVID-19.”2
References
1.Hayden F. Ensitrelvir to Prevent COVID-19 in Households: SCORPIO-PEP Phase III Placebo-Controlled Trial Results. Abstract 200. Presented at CROI 2025, San Francisco, CA: March 9-12, 2025.
3. Shionogi Announces Global Phase 3 Trial Demonstrates Post-Exposure Prophylactic Use of Ensitrelvir Prevents Symptomatic COVID-19. Shionogi press release. October 29, 2024. Accessed October 29, 2024.
https://www.shionogi.com/global/en/news/2024/10/20241029.html
