Ensitrelvir reduced symptomatic COVID-19 risk by 67% after household exposure in the Phase 3 SCORPIO-PEP trial and was generally well tolerated, according to data published in NEJM.
Written By: Nikita Jha, BPharm
Reviewed By: Pharmacally Editorial Team
Shionogi reported Phase 3 SCORPIO-PEP results showing that ensitrelvir significantly reduced the risk of symptomatic COVID-19 after household exposure to an infected individual. The findings were published in the New England Journal of Medicine.
The global, double-blind, randomized, placebo-controlled study evaluated ensitrelvir as post-exposure prophylaxis (PEP) in individuals aged 12 years and older who had household exposure to symptomatic COVID-19 and tested negative at enrollment. In the primary analysis population (n=2,041), symptomatic COVID-19 developed in 2.9% of ensitrelvir recipients versus 9.0% of placebo recipients by Day 10, representing a 67% relative risk reduction (risk ratio, 0.33; 95% CI, 0.22-0.49; P<0.0001).
A prespecified subgroup analysis in participants with one or more risk factors for severe disease showed a 76% relative risk reduction with ensitrelvir. Symptomatic COVID-19 occurred in 2.4% of participants receiving ensitrelvir compared with 9.9% in the placebo group (risk ratio, 0.24; 95% CI, 0.12-0.49).
Frederick Hayden, MD, Professor Emeritus of Clinical Virology and Medicine at the University of Virginia School of Medicine, said participants who received ensitrelvir within 72 hours after household exposure were about three times less likely to develop COVID-19 than those receiving placebo. He noted that the findings support the potential role of oral antivirals in preventing COVID-19, including in higher-risk individuals.
Ensitrelvir was generally well tolerated, with adverse event rates of 15.1% in the ensitrelvir group and 15.5% in the placebo group. Common treatment-emergent adverse events included headache, diarrhea, nasopharyngitis, cough, fatigue, and influenza-like illness. No treatment-related dysgeusia was reported.
The SCORPIO-PEP trial (NCT05897541) enrolled 2,387 participants across global study sites between June 2023 and September 2024. More than 98% of household contacts showed evidence of prior SARS-CoV-2 infection, vaccination, or both based on antibody testing. Participants were randomized 1:1 to receive ensitrelvir or placebo within 72 hours after symptom onset in the infected household contact. The ensitrelvir regimen included 375 mg on Day 1 followed by 125 mg daily on Days 2 through 5.
According to Shionogi, SCORPIO-PEP is the first Phase 3 trial of an oral antiviral to meet its primary endpoint for preventing COVID-19 following exposure to an infected individual.
Ensitrelvir is a SARS-CoV-2 main protease inhibitor co-developed by Hokkaido University and Shionogi, the antiviral selectively inhibits the viral protease required for SARS-CoV-2 replication.
Ensitrelvir is currently under review by the U.S. Food and Drug Administration for COVID-19 post-exposure prophylaxis, with a PDUFA target date of June 16, 2026. In Japan, the drug is approved as XOCOVA for COVID-19 treatment and post-exposure prevention.
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About the Writer
Nikita Jha, BPharm (LinkedIn) a pharmacy graduate specializing in medical writing, with a strong ability to interpret complex medical and regulatory information and translate it into clear, accurate, and evidence-based healthcare content. Known for her attention to detail and precision, she focuses on delivering high-quality scientific communication that supports drug safety and informed decision-making.