Patisiran: First Global Approval
Patisiran: First Global Approval
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DOI：
10.1007/s40265-018-0983-6
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发表时间：
2018-10-01
期刊：
影响因子：
11.5
通讯作者：
Hoy, Sheridan M.
中科院分区：
文献类型：
--
作者：
Hoy, Sheridan M.
Patisiran (ONPATTRO) 是一种双链小干扰 RNA，封装在脂质纳米颗粒中，用于递送至肝细胞。通过与突变型和野生型运甲状腺素蛋白 (TTR) 信使 RNA 的 3 个非翻译区中的遗传保守序列特异性结合，patisiran 导致其降解（通过 RNA 干扰），从而降低血清 TTR 蛋白水平和组织 TTR 蛋白沉积。 Patisiran 是由 Alnylam Pharmaceuticals 开发的；它最近在美国被批准用于治疗成人遗传性 TTR 介导的淀粉样变性 (hATTR) 的多发性神经病，随后在欧盟被批准用于治疗 1 期或 2 期多发性神经病成人的 hATTR。对于体重 < 100 kg 的患者，推荐剂量为每 3 周一次 0.3 mg/kg，持续约 80 分钟一次静脉输注；对于体重 >= 100 kg 的患者，每 3 周一次 30 mg/kg。本文总结了 patisiran 开发过程中导致这些批准的里程碑。
Patisiran (ONPATTRO) is a double-stranded small interfering RNA encapsulated in a lipid nanoparticle for delivery to hepatocytes. By specifically binding to a genetically conserved sequence in the 3 untranslated region of mutant and wild-type transthyretin (TTR) messenger RNA, patisiran causes its degradation (via RNA interference) and subsequently a reduction in serum TTR protein levels and tissue TTR protein deposits. Patisiran has been developed by Alnylam Pharmaceuticals; it was recently approved in the USA for the treatment of the polyneuropathy of hereditary TTR-mediated amyloidosis (hATTR) in adults and subsequently approved in the EU for the treatment of hATTR in adults with stage 1 or 2 polyneuropathy. The recommended dosage, administered as a single intravenous infusion over approximately 80 min, is 0.3 mg/kg once every 3 weeks for patients weighing < 100 kg and 30 mg once every 3 weeks for patients weighing >= 100 kg. This article summarizes the milestones in the development of patisiran leading to these approvals.