Olgotrelvir as a Single-Agent Treatment of Nonhospitalized Patients with Covid-19
M.D Rongmeng Jiang, M.Med Bing Han, M.D Wanhong Xu, Ph.D Xiaoying Zhang, B.Med Chunxian Peng, B.Med Qiang Dang, M.Med Wei Sun, M.D Ling Lin, M.Med Yuanlong Lin, Lingyan Fan, Dongqing Lv, M.D Lei Shao, M.Med Ying Chen, Yunqing Qiu, M.Med Limei Han, M.Med Weixiang Kong, B.Med Guangming Li, M.D Kai Wang, M.D Jie Peng, M.D Bingliang Lin, B.Med Zhaowei Tong, M.D Xiaobo Lu, M.Med Lifeng Wang, Feng Gao, B.Med Jiemei Feng, M.D Yongxia Li, M.Med Xiaojun Ma, M.D Jinxiang Wang, M.S Shanbo Wang, B.Med Wei Shen, M.Med Chao Wang, M.Med Kuan Yan, B.S Zhenhao Lin, Ph.D Can Jin, M.S Long Mao, M.S Jia Liu, Ph.D Yulia Kushnareva, Olivia Kotoi, Zhenhong Zhu, M.D Mike Royal, Ph.D Mark Brunswick, Ph.D Henry Ji, M.D Xiao Xu, M.D Hongzhou Lu
NEJM Evidence, doi:10.1056/evidoa2400026
BACKGROUND Olgotrelvir is an oral antiviral with dual mechanisms of action targeting severe acute respiratory syndrome coronavirus 2 main protease (i.e., M pro ) and human cathepsin L. It has potential to serve as a single-agent treatment of coronavirus disease 2019 (Covid-19). METHODS We conducted a phase 3, double-blind, randomized, placebo-controlled trial to evaluate the efficacy and safety of olgotrelvir in 1212 nonhospitalized adult participants with mild to moderate Covid-19, irrespective of risk factors, who were randomly assigned to receive orally either 600 mg of olgotrelvir or placebo twice daily for 5 days. The primary and key secondary end points were time to sustained recovery of a panel of 11 Covid-19-related symptoms and the viral ribonucleic acid (RNA) load. The safety end point was incidence of treatment-emergent adverse events.
RESULTS The baseline characteristics of 1212 participants were similar in the two groups. In the modified intention-to-treat population (567 patients in the placebo group and 558 in the olgotrelvir group), the median time to symptom recovery was 205 hours in the olgotrelvir group versus 264 hours in the placebo group (hazard ratio, 1.29; 95% confidence interval [CI], 1.13 to 1.46; P<0.001). The least squares mean (95% CI) changes of viral RNA load from baseline were -2.20 (-2.59 to -1.81) log 10 copies/ml in olgotrelvirtreated participants and -1.40 (-1.79 to -1.01) in participants receiving placebo at day 4. Skin rash (3.3%) and nausea (1.5%) were more frequent in the olgotrelvir group than in the placebo group; there were no treatment-related serious adverse events, and no deaths were reported.
Author Affiliations
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