Springer Nature, Mairangi Bay, Private Bag 65901, Auckland, 0754, New Zealand.
Drugs. 2021 May;81(7):875-879. doi: 10.1007/s40265-021-01512-2. Epub 2021 Apr 16.
Casimersen (Amondys 45™) is an antisense oligonucleotide of the phosphorodiamidate morpholino oligomer subclass developed by Sarepta Therapeutics for the treatment of Duchenne muscular dystrophy (DMD) in patients who have a mutation in the DMD gene that is amenable to exon 45 skipping. Administered by intravenous infusion, casimersen is designed to bind to exon 45 of the DMD gene pre-mRNA, resulting in skipping of this exon during mRNA processing, intended to allow for production of an internally truncated but functional dystrophin protein in patients with DMD. Casimersen received its first approval on 25 February 2021, in the USA, for the treatment of DMD in patients who have a confirmed mutation of the DMD gene that is amenable to exon 45 skipping. The approval, granted under the US FDA Accelerated Approval Program, was based on an observed increase in dystrophin production in skeletal muscle in patients treated with casimersen. Casimersen is continuing in phase III development for the treatment of DMD in several other countries worldwide. This article summarises the milestones in the development of casimersen leading to this first approval for DMD. As with other approvals under the Accelerated Approval Program, continued approval for this indication may be contingent upon verification of a clinical benefit in confirmatory trials.
卡司美生（Amondys 45™）是一种反义寡核苷酸，属于磷酰胺二酯吗啉代寡聚物亚类，由 Sarepta Therapeutics 公司研发，用于治疗 DMD 患者。这些患者的 DMD 基因突变可通过外显子 45 跳跃进行治疗。卡司美生通过静脉输注给药，旨在与 DMD 基因前 mRNA 的外显子 45 结合，从而在 mRNA 加工过程中外显子 45 跳跃，使 DMD 患者能够产生内部截断但有功能的抗肌萎缩蛋白。2021 年 2 月 25 日，卡司美生在美国首次获批，用于治疗 DMD 患者，这些患者的 DMD 基因突变可通过外显子 45 跳跃进行治疗。该批准是基于接受卡司美生治疗的患者骨骼肌中抗肌萎缩蛋白产量增加而获得的，是根据美国 FDA 的加速批准程序授予的。卡司美生正在全球多个国家进行治疗 DMD 的 III 期开发。本文总结了导致首次批准 DMD 的卡司美生开发的里程碑事件。与加速批准程序下的其他批准一样，对于该适应证的继续批准可能取决于在确证性试验中验证临床获益。
