Licari Amelia, Marseglia GianLuigi, Castagnoli Riccardo, Marseglia Alessia, Ciprandi Giorgio
University of Pavia, Foundation IRCCS Policlinico San Matteo, Department of Pediatrics , Pavia , Italy.
Expert Opin Drug Discov. 2015;10(9):1033-42. doi: 10.1517/17460441.2015.1048220. Epub 2015 May 15.
The evolution in immunological methods used to assess human allergic diseases has led to the identification of immunoglobulin E (IgE) as a diagnostic biomarker and a potential therapeutic target. Innovative technologies in molecular biology and immunogenetics contributed to the development of a selective blocking agent, disclosing new therapeutic perspectives in the treatment of allergic asthma. Omalizumab is the most advanced humanized anti-IgE monoclonal antibody that specifically binds serum-free IgE. Omalizumab also interrupts the allergic cascade by preventing binding of IgE with FcεRI receptors on mast cells, basophils, antigen-presenting cells and other inflammatory cells.
This review discusses the discovery strategy and preclinical development of omalizumab. Furthermore, it also provides a clinical overview of the key trials leading to its launch and a detailed analysis of safety and post-marketing data.
The clinical efficacy of omalizumab in allergic asthma has been well documented in clinical trials, involving adults, adolescents and children with moderate-to-severe and severe allergic asthma. To date, omalizumab has also been approved in chronic idiopathic urticaria for patients 12 years and older who remain symptomatic despite high dosages of H1 antihistamines. Omalizumab has also been investigated in many other different patient populations beyond allergic asthma and may yet have an application to other indications. While omalizumab is the only mAb available for treating allergic asthma, the authors anticipate that new mAbs will emerge in the future that overcome omalizumab's current limitations.
用于评估人类过敏性疾病的免疫学方法的发展，已使免疫球蛋白E（IgE）被鉴定为一种诊断生物标志物和潜在的治疗靶点。分子生物学和免疫遗传学的创新技术推动了一种选择性阻断剂的开发，为过敏性哮喘的治疗揭示了新的治疗前景。奥马珠单抗是最先进的人源化抗IgE单克隆抗体，它能特异性结合游离血清IgE。奥马珠单抗还通过阻止IgE与肥大细胞、嗜碱性粒细胞、抗原呈递细胞和其他炎症细胞上的FcεRI受体结合，中断过敏反应级联。
本综述讨论了奥马珠单抗的发现策略和临床前开发。此外，还提供了其上市前关键试验的临床概述以及对安全性和上市后数据的详细分析。
奥马珠单抗在过敏性哮喘中的临床疗效已在临床试验中得到充分证明，这些试验涉及患有中度至重度和重度过敏性哮喘的成人、青少年和儿童。迄今为止，奥马珠单抗也已被批准用于治疗12岁及以上、尽管使用高剂量H1抗组胺药仍有症状的慢性特发性荨麻疹患者。除过敏性哮喘外，奥马珠单抗还在许多其他不同患者群体中进行了研究，可能还会有其他适应症的应用。虽然奥马珠单抗是唯一可用于治疗过敏性哮喘的单克隆抗体，但作者预计未来会出现克服奥马珠单抗当前局限性的新单克隆抗体。
