• Zhujun Cao, Weiyi Gao, Hong Bao, Haiyan Feng, Shuya Mei, Peizhan Chen, Yueqiu Gao, Zhilei Cui, Qin Zhang, Xianmin Meng, Honglian Gui, Weijing Wang, Yimei Jiang, Zijia Song, Yiqing Shi, Jing Sun, Yifei Zhang, Qing Xie, Yiping Xu, Guang Ning, Yuan Gao, and Ren Zhao.
• From the Department of Infectious Diseases, Shanghai Institute of Virology (Z. Cao, H.G., W.W., Q.X.), the Department of Emergency Medicine, Shanghai Innovation Center for Digital Medicine (W.G.), the Clinical Research Center, Shanghai National Center for Translational Medicine, State Key Laboratory of Medical Genomics (P.C., Y.X.), the Departments of General Surgery (Y.J., Z.S., Y.S., R.Z.) and Gastroenterology (J.S.), the Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases (Y.Z., G.N.), and Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the People's Republic of China, Shanghai Key Laboratory for Endocrine Tumors (Y.Z., G.N.), Ruijin Hospital, the Department of Critical Care Medicine, Renji Hospital (S.M., Yuan Gao), the Department of Respiratory Medicine, Xinhua Hospital (Z. Cui), and the Department of Good Clinical Practice Office and Phase I Unit, Tongren Hospital (Q.Z.), Shanghai Jiao Tong University School of Medicine, the Department of Respiratory and Critical Medicine, Shanghai Pudong Hospital, Fudan University Pudong Medical Center (H.B.), the Departments of Pain Rehabilitation (H.F.) and Pharmacology (X.M.), Shanghai Public Health Clinical Center, Fudan University, and the Department of Liver Disease, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine (Yueqiu Gao) - all in Shanghai, China.
• N. Engl. J. Med. 2023 Feb 2; 388 (5): 406417406-417.

BackgroundNirmatrelvir-ritonavir has been authorized for emergency use by many countries for the treatment of coronavirus disease 2019 (Covid-19). However, the supply falls short of the global demand, which creates a need for more options. VV116 is an oral antiviral agent with potent activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).MethodsWe conducted a phase 3, noninferiority, observer-blinded, randomized trial during the outbreak caused by the B.1.1.529 (omicron) variant of SARS-CoV-2. Symptomatic adults with mild-to-moderate Covid-19 with a high risk of progression were assigned to receive a 5-day course of either VV116 or nirmatrelvir-ritonavir. The primary end point was the time to sustained clinical recovery through day 28. Sustained clinical recovery was defined as the alleviation of all Covid-19-related target symptoms to a total score of 0 or 1 for the sum of each symptom (on a scale from 0 to 3, with higher scores indicating greater severity; total scores on the 11-item scale range from 0 to 33) for 2 consecutive days. A lower boundary of the two-sided 95% confidence interval for the hazard ratio of more than 0.8 was considered to indicate noninferiority (with a hazard ratio of >1 indicating a shorter time to sustained clinical recovery with VV116 than with nirmatrelvir-ritonavir).ResultsA total of 822 participants underwent randomization, and 771 received VV116 (384 participants) or nirmatrelvir-ritonavir (387 participants). The noninferiority of VV116 to nirmatrelvir-ritonavir with respect to the time to sustained clinical recovery was established in the primary analysis (hazard ratio, 1.17; 95% confidence interval [CI], 1.01 to 1.35) and was maintained in the final analysis (median, 4 days with VV116 and 5 days with nirmatrelvir-ritonavir; hazard ratio, 1.17; 95% CI, 1.02 to 1.36). In the final analysis, the time to sustained symptom resolution (score of 0 for each of the 11 Covid-19-related target symptoms for 2 consecutive days) and to a first negative SARS-CoV-2 test did not differ substantially between the two groups. No participants in either group had died or had had progression to severe Covid-19 by day 28. The incidence of adverse events was lower in the VV116 group than in the nirmatrelvir-ritonavir group (67.4% vs. 77.3%).ConclusionsAmong adults with mild-to-moderate Covid-19 who were at risk for progression, VV116 was noninferior to nirmatrelvir-ritonavir with respect to the time to sustained clinical recovery, with fewer safety concerns. (Funded by Vigonvita Life Sciences and others; ClinicalTrials.gov number, NCT05341609; Chinese Clinical Trial Registry number, ChiCTR2200057856.).Copyright © 2022 Massachusetts Medical Society.

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