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Drugs. 2019 Feb;79(3):347-352. doi: 10.1007/s40265-019-01068-2.
Ravulizumab (ravulizumab-cwvz; ULTOMIRIS™), a humanized monoclonal antibody, is a complement C5 inhibitor developed by Alexion Pharmaceuticals for the treatment of paroxysmal nocturnal haemoglobinuria (PNH) and atypical haemolytic uraemic syndrome (aHUS). Like the first-generation C5 inhibitor, eculizumab, ravulizumab binds specifically and with high affinity to the complement protein C5, thereby preventing formation of the terminal complement complex C5b-9, which mediates cell lysis. In December 2018, intravenous ravulizumab received its first global approval in the USA for the treatment of adults with PNH, and is under regulatory review in the European Union and Japan in this indication. Phase 3 development of intravenous ravulizumab for the treatment of aHUS is underway worldwide. The use of ravulizumab in myasthenia gravis and IgA nephropathy is also being evaluated in the USA in early-phase and preclinical studies, respectively. Clinical development of a subcutaneous formulation for PNH and aHUS is also underway. Ravulizumab has been developed using Xencor's antibody half-life prolongation technology (Xtend™), which utilises antibody Fc variants to prolong half-life. Alexion is also evaluating the coadministration of subcutaneous ravulizumab with Halozyme's ENHANZE drug-delivery technology (rHuPH20), which may have the potential to further extend the dosing interval. This article summarizes the milestones in the development of ravulizumab leading to this first approval for PNH.
拉维珠单抗（ravulizumab-cwvz；ULTOMIRIS™）是一种人源化单克隆抗体，由 Alexion 制药公司开发，用于治疗阵发性夜间血红蛋白尿症（PNH）和非典型溶血尿毒综合征（aHUS）。与第一代 C5 抑制剂依库珠单抗一样，拉维珠单抗特异性和高亲和力地结合补体蛋白 C5，从而阻止末端补体复合物 C5b-9 的形成，该复合物介导细胞裂解。2018 年 12 月，静脉用拉维珠单抗在美国首次获得全球批准，用于治疗 PNH 成人患者，目前正在欧盟和日本进行该适应证的监管审查。全球范围内正在进行静脉用拉维珠单抗治疗 aHUS 的 3 期开发。在美国，早期和临床前研究分别评估了拉维珠单抗在重症肌无力和 IgA 肾病中的应用。用于 PNH 和 aHUS 的皮下制剂的临床开发也正在进行中。拉维珠单抗是利用 Xencor 的抗体半衰期延长技术（Xtend™）开发的，该技术利用抗体 Fc 变体来延长半衰期。Alexion 还在评估皮下注射拉维珠单抗与 Halozyme 的 ENHANZE 药物输送技术（rHuPH20）的联合用药，这可能有潜力进一步延长给药间隔。本文总结了拉维珠单抗开发过程中的重要里程碑，这些里程碑促成了该药在 PNH 方面的首次批准。
