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Drugs. 2018 Sep;78(13):1371-1376. doi: 10.1007/s40265-018-0968-5.
Ionis Pharmaceuticals and Akcea Therapeutics have developed inotersen (Tegsedi™), an antisense oligonucleotide inhibitor of mutant and wild-type human transthyretin (TTR), for the treatment of hereditary transthyretin amyloidosis (hATTR). Mutation of the TTR gene results in accumulation of TTR protein fragments as amyloid deposits throughout the organs in patients with hATTR, including the peripheral nervous system and the heart. Treatment with inotersen, which selectively binds to TTR mRNA, prevents the synthesis of TTR protein in the liver, thus reducing further amyloid deposition throughout the body. Subcutaneous administration of inotersen significantly reduced neurological progression and improved health-related quality of life in patients with hATTR and polyneuropathy in a phase III trial. Based on these results, inotersen was recently approved in the EU for the treatment of stage 1 or 2 polyneuropathy in adult patients with hATTR and is under evaluation in the USA and Canada for a similar indication. This article summarizes the milestones in the development of inotersen leading to this first approval.
Ionis 制药公司和 Akcea 治疗公司开发了反义寡核苷酸抑制剂——依洛瑟林（Tegsedi™），用于治疗遗传性转甲状腺素蛋白淀粉样变（hATTR）。TTR 基因突变导致 TTR 蛋白片段在 hATTR 患者的各个器官中积累，形成淀粉样沉积物，包括周围神经系统和心脏。依洛瑟林与 TTR mRNA 选择性结合，可阻止肝脏中 TTR 蛋白的合成，从而减少全身其他部位的淀粉样沉积。在一项 III 期临床试验中，皮下注射依洛瑟林可显著减缓 hATTR 伴多发性神经病患者的神经进展，并改善其健康相关生活质量。基于这些结果，依洛瑟林最近在欧盟获得批准，用于治疗 hATTR 成人患者的 1 期或 2 期多发性神经病，并且正在美国和加拿大进行类似适应证的评估。本文总结了导致这一首次批准的依洛瑟林开发过程中的重要里程碑。
