Convertino Irma, Ferraro Sara, Cappello Emiliano, Valdiserra Giulia, Bonaso Marco, Tuccori Marco
Unit of Pharmacology and Pharmacovigilance, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Unit of Adverse Drug Reactions Monitoring, Pisa University Hospital, Pisa, Italy.
Expert Opin Drug Discov. 2023 Mar;18(3):231-245. doi: 10.1080/17460441.2023.2170348. Epub 2023 Jan 24.
Direct-acting SARS-CoV-2 antiviral monoclonal antibodies have been an integral part of therapeutic strategies against COVID-19 pandemic. The monoclonal strategy was jeopardized by the emergence of new variants and resistant strains, making many monoclonal antibodies quickly obsolete. Nevertheless, a possible strategy consists in the use of antibody cocktails and the development of the cilgavimab + tixagevimab in combination is placed in this context.
In this review, we describe the development of the cilgavimab + tixagevimab cocktail, from pre-clinical to real-world evidence.
The pre-clinical and clinical development of cilgavimab + tixagevimab followed a similar path to that of the antibodies developed in the earlier stages of the pandemic. Both antibodies have been developed from convalescent plasma and have been shown to be effective in clinical trials in prophylaxis and in early therapy. This cocktail has found its position in therapy especially in immunocompromised subjects for whom vaccine prevention is not feasible. The cocktail strategy, together with a more stable pandemic situation, could ensure a certain longevity to the drug against resistance, especially when compared with that of other antibodies. Recently emerged Omicron sub-lineages have demonstrated the ability to escape this cocktail's activity and so the future of this treatment could be compromised.
直接作用的严重急性呼吸综合征冠状病毒2(SARS-CoV-2)抗病毒单克隆抗体一直是对抗新冠疫情治疗策略的重要组成部分。单克隆抗体策略因新变种和耐药菌株的出现而受到威胁,许多单克隆抗体很快就过时了。然而,一种可行的策略是使用抗体鸡尾酒疗法,在此背景下开发了西加韦单抗+替沙格韦单抗组合。
在本综述中,我们描述了西加韦单抗+替沙格韦单抗鸡尾酒疗法从临床前到真实世界证据的发展过程。
西加韦单抗+替沙格韦单抗的临床前和临床开发过程与疫情早期开发的抗体类似。这两种抗体均从康复者血浆中开发而来,并已在预防和早期治疗的临床试验中显示出有效性。这种鸡尾酒疗法在治疗中占据了一席之地,尤其是在无法进行疫苗预防的免疫功能低下的患者中。与其他抗体相比,鸡尾酒疗法策略以及更稳定的疫情形势可能确保该药物在对抗耐药性方面具有一定的持久性。最近出现的奥密克戎亚谱系已证明有能力逃避这种鸡尾酒疗法的活性,因此这种治疗方法的未来可能受到影响。