Ensitrelvir Prevents Household COVID-19 Transmission in Phase 3 Trial

In order to conduct a thorough assessment of the efficacy of the protease inhibitor drug in question, researchers conducted a large-scale international clinical trial involving rigorous inclusion criteria. For the purposes of the study, the focus was made on patients who were tested and found negative for SARS-CoV-2 at the point of enrolment in the trial yet had the disease among their family members.

In total, 2,041 qualified contacts were randomly assigned to treatment groups receiving an active drug (ensitrelvir) administered orally over five days (day 1 - 375 mg; days 2 to 5 – 125 mg daily) or placebo treatment within 72 hours of the initial symptom appearance of the index patient. The endpoint of the study was established as the incidence of clinical COVID-19 by day 10 post enrolment, with the definition including laboratory evidence of positivity (positive RT-PCR test results) and presence of one or several of 14 pre-specified symptoms for at least 48 hours.

Key findings:

• The population included in mITT had 2,041 individuals, with 1,030 being placed under the active ensitrelvir arm, 1,011 were in the placebo arm, where their average age was 42.4 years old.
• The proportion of individuals developing clinical COVID-19 in the ensitrelvir group at 10 days was significantly lower at 2.9% (30 out of 1,030) than the incidence rate of 9.0% (91 out of 1,011) in the placebo group.
• This is a very strong risk ratio of 0.33 (95% Confidence Interval [CI], 0.22 to 0.49; P < 0.001), which corresponds to a huge 67% decrease in the likelihood of symptomatic infection.
• Of the total subjects randomized, 71.1% of them were randomized quickly within 48 hours after the index person's symptom presentation, and 37.0% had one or more underlying chronic conditions that put them at increased risk of severe COVID-19.
• The overall incidence rate of adverse events caused by the treatment in the ensitrelvir and placebo groups was almost equal at 15.1% and 15.5%, respectively, and serious adverse events happened to be extremely rare, with the occurrence rate of only 0.2% in both groups.

In summary, this double-blind randomized clinical trial has proved the efficacy and safety of ensitrelvir when employed as a means of prophylaxis for protecting household contacts from being infected with coronavirus. The significant 67% reduction in symptomatic infections in absence of any serious adverse drug reactions makes up an important contribution to our antiviral defense strategy.

Reference:

Hayden, F. G., Shinkai, M., Clark, T. W., Luetkemeyer, A. F., Sax, P. E., Hanage, W. P., Gebo, K. A., Ikematsu, H., Izumikawa, K., Fukushi, A., Kezbor, S., Sakaguchi, H., Lacey, S., Ichihashi, G., Ohmagari, N., Uehara, T., & SCORPIO-PEP Study Team. (2026). Ensitrelvir for Covid-19 postexposure prophylaxis in household contacts. The New England Journal of Medicine, 394(19), 1905–1915. https://doi.org/10.1056/NEJMoa2509306