Division of Rheumatology, Allergy and Immunology, University of California, San Diego, CA, USA.
Institute of Allergology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Allergology and Immunology, Berlin, Germany.
Allergol Int. 2023 Jan;72(1):54-62. doi: 10.1016/j.alit.2022.06.001. Epub 2022 Jul 2.
Monoclonal antibodies (mAbs) have been shown to be effective and generally safe across a continually expanding list of therapeutic areas. We describe the advantages and limitations of mAbs as a therapeutic option compared with small molecules. Specifically, we discuss a novel mAb in the treatment of hereditary angioedema (HAE), a rare and potentially life-threatening condition characterized by recurrent unpredictable swelling attacks. HAE is mediated by dysregulation of plasma kallikrein activity leading to overproduction of bradykinin. Current prophylactic treatment for HAE includes androgens or replacement of the endogenous plasma kallikrein inhibitor, C1 inhibitor. However, there remains an unmet need for an effective, less burdensome treatment option. Lanadelumab is a fully human mAb targeting plasma kallikrein. Results from clinical trials, including a pivotal Phase 3 study and its ensuing open-label extension study, demonstrated that lanadelumab is associated with few treatment-related adverse events and reduced the rate of HAE attacks. This novel treatment option has the potential to significantly improve the lives of patients with HAE.
单克隆抗体（mAbs）在不断扩大的治疗领域中已被证明是有效且通常安全的。与小分子相比，我们描述了 mAbs 作为治疗选择的优势和局限性。具体来说，我们讨论了一种新型 mAb 在遗传性血管性水肿（HAE）治疗中的应用，这是一种罕见且可能危及生命的疾病，其特征是反复发作的不可预测的肿胀发作。HAE 是由血浆激肽释放酶活性失调引起的，导致缓激肽过度产生。目前 HAE 的预防性治疗包括雄激素或替代内源性血浆激肽释放酶抑制剂 C1 抑制剂。然而，仍需要一种有效、负担更小的治疗选择。Lanadelumab 是一种针对血浆激肽释放酶的全人源 mAb。临床试验结果，包括一项关键的 3 期研究及其随后的开放标签扩展研究，表明 lanadelumab 与较少的治疗相关不良事件相关，并降低了 HAE 发作的频率。这种新型治疗选择有可能显著改善 HAE 患者的生活。
