Bender Ignacio Rachel A, Chew Kara W, Moser Carlee, Currier Judith S, Eron Joseph J, Javan Arzhang Cyrus, Giganti Mark J, Ritz Justin, Gibbs Michael, Kouekam Hervé Tchouakam, Esser Mark T, Daar Eric S, Choudhary Manish, Deo Rinki, Fletcher Courtney V, Li Jonathan Z, Hughes Michael D, Smith Davey, Wohl David Alain
Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, WA, USA.
Vaccine and Infectious Disease Division, Fred Hutch Cancer Center, Seattle, WA, USA.
iScience. 2025 Feb 4;28(3):111938. doi: 10.1016/j.isci.2025.111938. eCollection 2025 Mar 21.
Monoclonal antibodies have potential as rapidly developable agents for treatment and prevention of emerging viruses. The ACTIV-2 trial randomized persons with mild-moderate COVID-19 to the monoclonal antibody combination tixagevimab/cilgavimab via intramuscular injection (600 mg IM) or infusion (300 mg IV) versus placebo. We present final safety and laboratory outcomes; primary outcomes were previously reported. The analyzed IM group included 214 participants, and the IV group, 106 participants. Adverse events were not different between treatment and placebo. The half-life of both components was >90 days for IM or 75 days for IV. New anti-drug antibodies were about 3 times more likely in active vs. placebo recipients. SARS-CoV-2 neutralizing antibodies increased 157-fold at 7 days and 127-fold at 1 month (IM-treated) but were less robust in IV participants. These data can inform future development of monoclonal antibodies against SARS-CoV-2 and other viruses, even if this intervention is of low utility for contemporary SARS-CoV-2 variants.
单克隆抗体有潜力成为快速开发的用于治疗和预防新出现病毒的药物。ACTIV-2试验将轻至中度新冠肺炎患者随机分为两组，一组通过肌肉注射（600毫克肌肉注射）或静脉输注（300毫克静脉注射）接受单克隆抗体组合替沙格韦单抗/西加韦单抗，另一组接受安慰剂。我们展示最终的安全性和实验室结果；主要结果此前已报告。分析的肌肉注射组包括214名参与者，静脉注射组包括106名参与者。治疗组和安慰剂组的不良事件无差异。两种成分的半衰期，肌肉注射组>90天，静脉注射组为75天。接受活性药物治疗的患者产生新抗药物抗体的可能性约为接受安慰剂治疗患者的3倍。严重急性呼吸综合征冠状病毒2（SARS-CoV-2）中和抗体在第7天增加157倍，在第1个月增加127倍（肌肉注射治疗组），但在静脉注射组中反应较弱。这些数据可为未来抗SARS-CoV-2和其他病毒单克隆抗体的开发提供参考，即使这种干预措施对当代SARS-CoV-2变体效用较低。
