A RECENT clinical trial has demonstrated the efficacy of ensitrelvir, an oral SARS-CoV-2 3CL protease inhibitor, in reducing the risk of COVID-19 in household contacts (HHC) of infected individuals when administered within 72 hours of symptom onset.
The SCORPIO-PEP study was a double-blind, placebo-controlled trial conducted across multiple countries, including the USA and Japan. HHC with a negative SARS-CoV-2 test were randomly assigned in a 1:1 ratio to receive either ensitrelvir (375 mg on Day 1, followed by 125 mg daily for 4 days) or a placebo. The primary analysis focused on those who were confirmed SARS-CoV-2-negative by central laboratory RT-PCR at baseline, evaluating the proportion who developed COVID-19 by Day 10. A secondary analysis included all participants, regardless of initial RT-PCR results.
Among the 2,389 enrolled participants, 2,041 met the criteria for the primary analysis (ensitrelvir: n=1,030; placebo: n=1,011). In this group, COVID-19 incidence was significantly lower in the ensitrelvir arm (2.9%) compared to placebo (9.0%), with a risk ratio of 0.33 (95% CI: 0.22–0.49; p<0.0001). Similar efficacy was observed in the broader intent-to-treat population, with a risk ratio of 0.43 (95% CI: 0.32–0.59; p<0.0001). Among participants already positive at baseline, the risk ratio was 0.75 (95% CI: 0.46–1.23). The rates of treatment-emergent adverse events were comparable between ensitrelvir and placebo groups (15.1% vs. 15.5%), with headache (2.9% vs. 2.5%), diarrhoea (1.8% vs. 1.3%), and influenza (1.1% vs. 1.6%) being the most common. No COVID-19-related hospitalisations or fatalities occurred.
Ensitrelvir demonstrated strong efficacy in reducing COVID-19 transmission among household contacts and was well tolerated, supporting its potential as a post-exposure prophylaxis option.
Reference
Fukushi A et al. Ensitrelvir to prevent COVID-19 in households: SCORPIO-PEP Phase III placebo-controlled trial results. Abstract 200. Conference on Retroviruses and Opportunistic Infections (CROI), March 9-12, 2025
