Oral Simnotrelvir for Adult Patients with Mild-to-Moderate Covid-19
Bin Cao, Yeming Wang, Hongzhou Lu, Chaolin Huang, Yumei Yang, Lianhan Shang, Chen Zhu, Rongmeng Jiang, Yihe Liu, Ling Lin, Ping Peng, Fuxiang Wang, Fengyun Gong, Honglin Hu, Cong Cheng, Xiangyang Yao, Xianwei Ye, Hourong Zhou, Yinzhong Shen, Chenfan Liu, Chunying Wang, Zhennan Yi, Bijie Hu, Jiuyang Xu, Xiaoying Gu, Jingshan Shen, Yechun Xu, Leike Zhang, Jia Fan, Renhong Tang, Chen Wang
Abstract
BACKGROUND: Simnotrelvir is an oral 3-chymotrypsin-like protease inhibitor that has been found to have in vitro activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and potential efficacy in a phase 1B trial. METHODS: In this phase 2-3, double-blind, randomized, placebo-controlled trial, we assigned patients who had mild-to-moderate coronavirus disease 2019 (Covid-19) and onset of symptoms within the past 3 days in a 1:1 ratio to receive 750 mg of simnotrelvir plus 100 mg of ritonavir or placebo twice daily for 5 days. The primary efficacy end point was the time to sustained resolution of symptoms, defined as the absence of 11 Covid-19-related symptoms for 2 consecutive days. Safety and changes in viral load were also assessed. RESULTS: copies per milliliter; 95% CI, -1.79 to -1.24). The incidence of adverse events during treatment was higher in the simnotrelvir group than in the placebo group (29.0% vs. 21.6%). Most adverse events were mild or moderate. CONCLUSIONS: Early administration of simnotrelvir plus ritonavir shortened the time to the resolution of symptoms among adult patients with Covid-19, without evident safety concerns. (Funded by Jiangsu Simcere Pharmaceutical; ClinicalTrials.gov number, NCT05506176.).