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Drugs. 2019 Jul;79(11):1255-1262. doi: 10.1007/s40265-019-01162-5.
Onasemnogene abeparvovec (onasemnogene abeparvovec-xioi; formerly AVXS-101; ZOLGENSMA) is an adeno-associated viral vector-based gene therapy designed to deliver a functional copy of the human survival motor neuron (SMN) gene to the motor neuron cells of patients with spinal muscular atrophy (SMA). It has been developed by AveXis, a Novartis company, and was approved in May 2019 in the USA for the treatment of paediatric patients aged < 2 years with SMA and bi-allelic mutations in the SMN1 gene (the primary gene encoding survival motor neuron protein). Onasemnogene abeparvovec is the first gene therapy to be approved for SMA in the USA. The recommended dose is 1.1 × 10 vector genomes per kg of bodyweight, administered as a single intravenous infusion over 60 min. Regulatory assessments for this formulation of onasemnogene abeparvovec are underway in the EU and Japan; an intrathecal formulation is currently undergoing clinical development in the USA. This article summarizes the milestones in the development of onasemnogene abeparvovec leading to this first approval for the treatment of paediatric patients aged < 2 years with SMA and bi-allelic mutations in SMN1.
Onasemnogene abeparvovec（onasemnogene abeparvovec-xioi； formerly AVXS-101； ZOLGENSMA）是一种基于腺相关病毒载体的基因治疗药物，旨在将功能性人类生存运动神经元（SMN）基因递送到脊髓性肌萎缩症（SMA）患者的运动神经元细胞中。它由诺华公司的 AveXis 开发，于 2019 年 5 月在美国获得批准，用于治疗年龄<2 岁的 SMA 患儿和 SMN1 基因双等位基因突变患者（该基因是编码生存运动神经元蛋白的主要基因）。Onasemnogene abeparvovec 是美国批准的首个用于治疗 SMA 的基因治疗药物。推荐剂量为 1.1×10 个载体基因组/公斤体重，作为单次静脉输注在 60 分钟内完成。这种制剂的监管评估正在欧盟和日本进行；鞘内制剂目前正在美国进行临床开发。本文总结了导致这种针对年龄<2 岁的 SMA 患儿和 SMN1 基因双等位基因突变患者的治疗方法的首次批准的 Onasemnogene abeparvovec 开发的里程碑事件。
