Matching-adjusted comparison of the effectiveness and safety of Ensitrelvir versus Remdesivir for high-risk, hospitalized patients with non-severe COVID-19 in Japan.

BACKGROUND: Ensitrelvir (ESV) is approved in Japan for the treatment of mild to moderate COVID-19 in standard-risk patients; however, real-world evidence regarding outcomes among hospitalized high-risk patients remains limited. We evaluated whether oral ESV could serve as a feasible alternative to intravenous remdesivir (RDV).

METHODS: We conducted a retrospective multicenter cohort study of hospitalized patients with mild to moderate COVID-19 and at least one risk factor for disease progression treated with ESV or RDV between June 2023 and March 2024 at two hospitals in Japan. Patients unable to receive oral therapy were excluded. Propensity score matching adjusted for baseline differences. The primary outcome was a composite of disease progression or all-cause mortality within 28 days.

RESULTS: Among 207 patients, 44 received ESV and 163 received RDV. In the overall cohort, the composite outcome occurred in 4 vs. 10 patients (P = 0.49). After matching, 40 patients were included in each group; all patients in the matched cohort had mild disease without oxygen requirement. In the matched cohort, the composite outcome occurred in 4 patients in each group (P > 0.99). Individual components showed no significant differences (mortality: 4 vs. 3; progression: 2 vs. 2).

CONCLUSIONS: In this multicenter cohort of hospitalized high-risk patients with mild to moderate COVID-19 able to receive oral therapy, no significant differences were observed between ESV and RDV in the matched cohort of patients with mild disease. ESV may represent a feasible oral alternative in selected high-risk patients able to receive oral therapy.