Research Division, Chugai Pharmaceutical Co., Ltd., 1-135 Komakado, Gotemba, Shizuoka, 412-8513, Japan.
Department of Pediatrics, Nara Medical University, Kashihara, Nara, Japan.
Int J Hematol. 2020 Jan;111(1):20-30. doi: 10.1007/s12185-018-2545-9. Epub 2018 Oct 22.
Hemophilia A is a congenital disorder caused by deficiency or malfunction of coagulation factor (F) VIII. While exogenously provided FVIII effectively reduces bleeding complications in many hemophilia A patients, multiple efforts are underway to develop new drugs to meet the needs that conventional FVIII agents do not. We have been long engaged in creating and clinically developing a humanized anti-FIXa/FX asymmetric bispecific IgG antibody with a FVIIIa-cofactor activity. Since this project was born from a creative and unique idea, our group recognized from the first that it would face many difficulties in the course of research including establishment of industrial manufacturability of an asymmetric bispecific IgG antibody. The group actually faced various challenges, but addressed all of them during about 10 years of research, and successfully created the potent humanized bispecific antibody, emicizumab. Emicizumab has showed clinical benefits in the human trials among which the first one was started in 2012, and has been currently approved in US, EU, Japan, and some other countries. It is now expected to improve the quality of life of patients and their families. In this article, we review the course of the research and clinical development of emicizumab, and describe its molecular characteristics.
血友病 A 是一种由凝血因子（F）VIII 缺乏或功能异常引起的先天性疾病。虽然外源性提供的 FVIII 有效地减少了许多血友病 A 患者的出血并发症，但正在进行多项努力来开发新的药物以满足传统 FVIII 制剂无法满足的需求。我们一直致力于创造和临床开发具有 FVIIIa 辅助因子活性的人源化抗 FIXa/FX 不对称双特异性 IgG 抗体。由于这个项目源于一个富有创意和独特的想法，我们的团队从一开始就认识到，在研究过程中，包括建立不对称双特异性 IgG 抗体的工业可制造性方面，它将面临许多困难。该团队实际上面临着各种挑战，但在大约 10 年的研究中成功地解决了所有这些问题，并成功地创建了有效的人源化双特异性抗体emicizumab。Emicizumab 在 2012 年开始的首次人体试验中显示出了临床益处，并已在美国、欧盟、日本和其他一些国家获得批准。它现在有望提高患者及其家属的生活质量。本文回顾了 emicizumab 的研究和临床开发过程，并描述了其分子特征。
