Ensitrelvir Shows Promise as Effective COVID-19 Antiviral in Phase 2 Trial
Covid-19 Now Endemic in India
A new study published in the journal of The Lancet Infectious Diseases showed that an efficient substitute for current COVID-19 therapies is ensitrelvir, a once-daily oral SARS-CoV-2 protease inhibitor developed by Shionogi. The current oral first-line medication for COVID-19, ritonavir-boosted nirmatrelvir, shares a molecular target (the primary protease) with ensitrelvir. Thus, this study was set to compare the clinical antiviral effects of these two medications.
Low-risk people between the ages of 18 and 60 who had early symptoms of COVID-19 (less than four days) were assessed in this study in Thailand and Laos. One of eight groups (oral ensitrelvir, ritonavir-boosted nirmatrelvir (both for five days), or no treatment) was given to each participant. SARS-CoV-2 viral clearance rate from day 0 to day 5, measured in a modified intention-to-treat population, was the main outcome.
4 oropharyngeal swabs were taken on day 0, two per day on days 1–7, and once more on days 10 and 14. A Bayesian hierarchical linear model based on 14 paired samples was used to evaluate viral clearance. To account for time-related effects, a meta-analysis of individual patient data from every small molecule treatment available on this platform was also carried out.
Of the 903 patients enrolled between March 17, 2023, and April 21, 2024, 604 were simultaneously allocated to the 3 therapy groups (ensitrelvir n = 202; ritonavir-boosted nirmatrelvir n = 207; no study medication n = 195). The median estimated half-lives for SARS-CoV-2 clearance were 5·9 h (IQR 4·0–8·6) for ensitrelvir, 5·2 h (3·8–6·6) for nirmatrelvir, and 11·6 h (8·1–14·5) for no study medication.
Viral clearance after ensitrelvir was 16% slower (5–25) than ritonavir-boosted nirmatrelvir and 82% quicker (95% credible interval 61–104) than no study medication. Nirmatrelvir and ensitrelvir exhibited the greatest antiviral effects (1157 patients) in the meta-analysis of all unblinded small molecule medications assessed in the platform study.
10 (5%) out of 202 patients in the ensitrelvir group and 15 (7%) out of 207 patients in the nirmatrelvir group experienced a viral rebound (p=0·45). Overall, ensitrelvir and nirmatrelvir both speed up the removal of SARS-CoV-2 viruses from the oropharynx. When treating COVID-19, ensitrelvir is a useful substitute for the antivirals that are already on the market.
Source:
Schilling, W. H. K., Jittamala, P., Wongnak, P., Watson, J. A., Boyd, S., Luvira, V., Siripoon, T., Ngamprasertchai, T., Batty, E. M., Beer, E., Singh, S., Asawasriworanan, T., Seers, T., Phommasone, K., Evans, T. J., Kruabkontho, V., Ngernseng, T., Tubprasert, J., Abdad, M. Y., … PLATCOV Collaborative Group. (2025). Antiviral efficacy of oral ensitrelvir versus oral ritonavir-boosted nirmatrelvir in COVID-19 (PLATCOV): an open-label, phase 2, randomised, controlled, adaptive trial. The Lancet Infectious Diseases. https://doi.org/10.1016/S1473-3099(25)00482-7
