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. 2025 Jun;14(6):1287-1297.
doi: 10.1007/s40121-025-01156-9. Epub 2025 Apr 19.

Ensitrelvir in Hospitalized Patients with SARS-CoV-2 During the Omicron Epidemic: A Single-Center Observational Study

Masaya Yamato  1 , Masahiro Kinoshita  2 , Yuki Yoshida  3 , Yudai Yamamoto  1 , Rie Izuhara  4 , Takuhiro Sonoyama  5
Affiliations

Ensitrelvir in Hospitalized Patients with SARS-CoV-2 During the Omicron Epidemic: A Single-Center Observational Study

Masaya Yamato et al. Infect Dis Ther. 2025 Jun.

Abstract

Introduction: Ensitrelvir, a novel oral 3C-like protease inhibitor targeting severe acute respiratory syndrome coronavirus 2, has been available in Japan since November 2022. This report presents patient characteristics and treatment outcomes of patients receiving ensitrelvir with comparison to remdesivir during the same period.

Methods: A single-center chart review was conducted at Rinku General Medical Center, one of four designated medical institutions for specific infectious diseases in Japan. All hospitalized patients with coronavirus disease 2019 (COVID-19) between November 2022 and August 2024 who received either ensitrelvir or remdesivir in accordance with the on-label dosage and administration were included in the review. Information on patient background, severity of COVID-19, mortality after initiation of either treatment, post-treatment virologic outcomes, and clinical outcomes were collected from electronic records. Day 28 mortality, time to discharge, and time to viral clearance were calculated with and without adjustment using the inverse probability of treatment weighting (IPTW) method.

Results: During the study period, 156 patients received ensitrelvir and 337 received remdesivir as initial treatments, with average ages of 76.8 and 75.7 years, respectively. For baseline severity, 24.4% of ensitrelvir recipients and 50.7% of remdesivir recipients had moderate to severe COVID-19. All-cause mortality at day 28 was 1.9% for ensitrelvir and 5.9% for remdesivir and the hazard ratio was 0.32 (95% CI 0.09-1.07). All-cause mortality after IPTW adjustment was 3.8% and 5.7%, respectively, and the hazard ratio was 0.66 (95% CI 0.19-2.29). Time to discharge was shorter with ensitrelvir, and viral clearance was similar between groups.

Conclusion: Ensitrelvir demonstrated a low day 28 mortality, even among patients with advanced age, immunosuppressive conditions, and moderate to severe COVID-19. These findings may suggest a potential role for ensitrelvir in the treatment of hospitalized patients with COVID-19.

Trial registration: This study was registered in UMIN Clinical Trials Registry (study ID UMIN000056047).

Keywords: COVID-19; Ensitrelvir; Mortality; Remdesivir; SARS-CoV-2; Time to discharge; Time to viral clearance.

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Conflict of interest statement

Declarations. Conflict of Interest: Masaya Yamato has received lecture fees from, and serves as an advisor for, Shionogi & Co., Ltd. Masahiro Kinoshita, Yuki Yoshida, and Takuhiro Sonoyama are employees of Shionogi & Co., Ltd.. Yudai Yamamoto and Rie Izuhara have no conflicts of interest to disclose. Ethical Approval: The study was conducted in accordance with the Declaration of Helsinki, and the Ethical Guidelines for Life Sciences and Medical Research Involving Human Subjects. The research protocol was reviewed and approved by the Rinku General Medical Center Clinical Research Ethics Committee (2-23 Rinku Ourai-Kita, Izumisano, Osaka 598-8577, Japan; protocol ID 2024FY-I-003; date of approval 20 August 2024). Patient consent was acquired using an opt-out procedure and no data were included that would allow identification of individual patients.

Figures

Fig. 1
Fig. 1
Patient disposition flowchart
Fig. 2
Fig. 2
Kaplan–Meier of day 28 all-cause mortality (a non-adjusted, b IPTW-adjusted). 95% confidence bands are shown. Unit of time is days. IPTW inverse probability of treatment weighting
Fig. 3
Fig. 3
Kaplan–Meier for time to viral clearance up to day 14 (a non-adjusted, b IPTW-adjusted). 95% confidence bands are shown. Unit of time is days. IPTW inverse probability of treatment weighting
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