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N Engl J Med
. 2024 Jan 18;390(3):230-241.
doi: 10.1056/NEJMoa2301425. Oral Simnotrelvir for Adult Patients with Mild-to-Moderate Covid-19
Bin Cao 1 , Yeming Wang 1 , Hongzhou Lu 1 , Chaolin Huang 1 , Yumei Yang 1 , Lianhan Shang 1 , Zhu Chen 1 , Rongmeng Jiang 1 , Yihe Liu 1 , Ling Lin 1 , Ping Peng 1 , Fuxiang Wang 1 , Fengyun Gong 1 , Honglin Hu 1 , Cong Cheng 1 , Xiangyang Yao 1 , Xianwei Ye 1 , Hourong Zhou 1 , Yinzhong Shen 1 , Chenfan Liu 1 , Chunying Wang 1 , Zhennan Yi 1 , Bijie Hu 1 , Jiuyang Xu 1 , Xiaoying Gu 1 , Jingshan Shen 1 , Yechun Xu 1 , Leike Zhang 1 , Jia Fan 1 , Renhong Tang 1 , Chen Wang 1
Affiliations
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: A total of 1208 patients were enrolled at 35 sites in China; 603 were assigned to receive simnotrelvir and 605 to receive placebo. Among patients in the modified intention-to-treat population who received the first dose of trial drug or placebo within 72 hours after symptom onset, the time to sustained resolution of Covid-19 symptoms was significantly shorter in the simnotrelvir group than in the placebo group (180.1 hours [95% confidence interval {CI}, 162.1 to 201.6] vs. 216.0 hours [95% CI, 203.4 to 228.1]; median difference, -35.8 hours [95% CI, -60.1 to -12.4]; P = 0.006 by Peto-Prentice test). On day 5, the decrease in viral load from baseline was greater in the simnotrelvir group than in the placebo group (mean difference [±SE], -1.51±0.14 log10 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.).
. 2024 Jan 18;390(3):230-241.
doi: 10.1056/NEJMoa2301425. Oral Simnotrelvir for Adult Patients with Mild-to-Moderate Covid-19
Bin Cao 1 , Yeming Wang 1 , Hongzhou Lu 1 , Chaolin Huang 1 , Yumei Yang 1 , Lianhan Shang 1 , Zhu Chen 1 , Rongmeng Jiang 1 , Yihe Liu 1 , Ling Lin 1 , Ping Peng 1 , Fuxiang Wang 1 , Fengyun Gong 1 , Honglin Hu 1 , Cong Cheng 1 , Xiangyang Yao 1 , Xianwei Ye 1 , Hourong Zhou 1 , Yinzhong Shen 1 , Chenfan Liu 1 , Chunying Wang 1 , Zhennan Yi 1 , Bijie Hu 1 , Jiuyang Xu 1 , Xiaoying Gu 1 , Jingshan Shen 1 , Yechun Xu 1 , Leike Zhang 1 , Jia Fan 1 , Renhong Tang 1 , Chen Wang 1
Affiliations
- PMID: 38231624
- DOI: 10.1056/NEJMoa2301425
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: A total of 1208 patients were enrolled at 35 sites in China; 603 were assigned to receive simnotrelvir and 605 to receive placebo. Among patients in the modified intention-to-treat population who received the first dose of trial drug or placebo within 72 hours after symptom onset, the time to sustained resolution of Covid-19 symptoms was significantly shorter in the simnotrelvir group than in the placebo group (180.1 hours [95% confidence interval {CI}, 162.1 to 201.6] vs. 216.0 hours [95% CI, 203.4 to 228.1]; median difference, -35.8 hours [95% CI, -60.1 to -12.4]; P = 0.006 by Peto-Prentice test). On day 5, the decrease in viral load from baseline was greater in the simnotrelvir group than in the placebo group (mean difference [±SE], -1.51±0.14 log10 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.).