| 近日，新药Exondys 51(eteplirsen)注射剂，成为首个获美国FDA批准治疗杜氏肌营养不良症(DMD)的药物。 Exondys 51(eteplirsen)专门适用于抗肌营养不良蛋白基因(dystrophin gene)中存在确证突变可导致51号外显子跳跃(exon 51 skipping)的DMD患者;据估计，该类患者约占全部DMD患者的13%。Exondys 51可解决导致该类DMD病例的根本病因，能够产生有功能的抗肌营养不良蛋白，在临床研究中具有广泛良好的安全性、耐受性和疗效。 FDA药物评价及研究中心主任Janet Woodcock表示，此次批准，使DMD群体中一类特殊类型的患者获得了一种重要的治疗选择，标志着DMD临床治疗的一个重大突破;我们将继续利用从药物Exondys 51中获得的科学认识，加速靶向抗肌营养不良蛋白基因其他外显子的新药研发，最终目的是有一天能够治疗携带所有导致外显子跳跃的确证基因突变的DMD患者。 批准日期：2016年9月26日 公司：Sarepta Therapeutics, Inc. EXONDYS 51（eteplirsen）注射剂，用于静脉内使用 最初美国批准：2016年 作用机理 Eteplirsen被设计成结合到外显子的肌营养不良蛋白51 mRNA前，导致这个外显子的排斥mRNA加工过程中的患者中适合的基因突变外显子51跳跃。外显子跳跃旨在允许生产内部截断抗肌萎缩蛋白，它是在研究2评估和研究3[见临床研究。 适应症和用法 EXONDYS 51是在谁拥有DMD基因是适合于外显子51跳跃的证实突变患者的治疗杜氏肌营养不良症（DMD）的指示反义寡核苷酸。根据与EXONDYS 51治疗的一些患者观察骨骼肌增加抗肌萎缩蛋白加速审批核准[见临床研究]。EXONDYS 51的临床效益尚未建立。这个指示继续批准可不经确证试验临床获益的核查队伍。 用法用量 每公斤体重每周一次的30公斤毫克 管理作为静脉内输注在35至60分钟 在给药前需要稀释 剂型和规格 注射： 100毫克/2毫升（50毫克/毫升）在单剂量小瓶 500毫克/10毫升（50毫克/毫升）在单剂量小瓶 禁忌症 无 不良反应 最常见的不良反应（发生率≥35％和高于安慰剂）为平衡障碍和呕吐。 包装规格/储存与处理 附送EXONDYS51注射单剂量小瓶提供。该溶液是无色透明的，并且可以具有一些乳光。 100毫克/2毫升的单剂量小瓶（50毫克/毫升）eteplirsen NDC60923-363-02 500毫克/10毫升（50毫克/毫升）eteplirsen单剂量小瓶 NDC60923-284-10 储存和处理 储存在2℃EXONDYS51〜8°C（36°F至46°F）。不要冻结。从光存储及保护EXONDYS51的原装硬纸盒，直到准备使用 Exondys 51(Eteplirsen) injection EXONDYS 51™ (eteplirsen), a therapy aimed at skipping exon 51 of the DMD gene involved in Duchenne muscular dystrophy (DMD), has received accelerated approval in the United States. General Information Exondys 51 (eteplirsen) is an antisense oligonucleotid designed to bind to exon 51 of dystrophin pre-mRNA. This results in exclusion of this exon during mRNA processing in patients with genetic mutations that are amenable to exon 51 skipping. Exon skipping is intended to allow for production of an internally truncated dystrophin protein. Exondys 51 is specifically indicated for the treatment of Duchenne muscular dystrophy (DMD) in patients who have a confirmed mutation of the DMD gene that is amenable to exon 51 skipping. Exondys 51 is supplied as an injection for intravenous administration. The recommended dose of Exondys 51 is 30 milligrams per kilogram administered once weekly as a 35 to 60 minute intravenous infusion. If a dose is missed, it may be administered as soon as possible after the scheduled time. Clinical Results FDA Approval Exondys 51 was granted accelerated approval based on an increase in dystrophin in skeletal muscle observed in some patients treated with Exondys 51. A clinical benefit of Exondys 51 has not been established. Continued approval for this indication may be contingent upon verification of a clinical benefit in confirmatory trial. Exondys 51 was evaluated in three clinical studies in patients who have a confirmed mutation of the DMD gene that is amenable to exon 51 skipping. In Study 1, patients were randomized to receive weekly infusions of Exondys 51 (30 mg/kg, n=4); Exondys 51 (50 mg/kg, n=4), or placebo (n=4) for 24 weeks. The primary endpoint was dystrophin production; a clinical outcome measure, the 6-minute walk test (6MWT), was also assessed. Patients had a mean age of 9.4 years, a mean 6-minute walk distance (6MWD) at baseline of 363 meters, and were on a stable dose of corticosteroids for at least 6 months. There was no significant difference in change in 6MWD between patients treated with Exondys 51 and those treated with placebo. All 12 patients who participated in Study 1 continued treatment with open-label Exondys 51 weekly for an additional 4 years in Study 2. The 4 patients who had been randomized to placebo were re-randomized 1:1 to Exondys 30 or 50 mg/kg/week such that there were 6 patients on each dose. Patients who participated in Study 2 were compared to an external control group. The primary clinical efficacy outcome measure was the 6MWT. Eleven patients in Study 2 had a muscle biopsy after 180 weeks of treatment with Exondys 51, which was analyzed for dystrophin protein level by Western blot. Study 2 failed to provide evidence of a clinical benefit of Exondys51 compared to the external control group. The average dystrophin protein level after 180 weeks of treatment with Exondys 51 was 0.93% of the dystrophin level in healthy subjects. Because of insufficient information on dystrophin protein levels before treatment with Exondys 51 in Study 1, it was not possible to estimate dystrophin production in response to Exondys 51 in Study 1. In Study 3, 13 patients were treated with open-label Exondys 51 (30 mg/kg) weekly for 48 weeks and had a muscle biopsy at baseline and after 48 weeks of treatment. Patients had a mean age of 8.9 years and were on a stable dose of corticosteroids for at least 6 months. Dystrophin levels in muscle tissue were assessed by Western blot. In the 12 patients with evaluable results, the pre-treatment dystrophin level was 0.16% ± 0.12% (mean ± standard deviation) of the dystrophin level in a healthy subject and 0.44% ± 0.43% after 48 weeks of treatment with Exondys 51 (p < 0.05). The median increase after 48 weeks was 0.1%. Side Effects Adverse effects associated with the use of Exondys 51 may include, but are not limited to, the following: balance disorder vomiting Mechanism of Action Exondys 51 (eteplirsen) is an antisense oligonucleotid designed to bind to exon 51 of dystrophin pre-mRNA. This results in exclusion of this exon during mRNA processing in patients with genetic mutations that are amenable to exon 51 skipping. Exon skipping is intended to allow for production of an internally truncated dystrophin protein. Additional Information For additional information regarding Exondys 51 or Duchenne muscular dystrophy (DMD) in patients who have a confirmed mutation of the DMD gene that is amenable to exon 51 skipping: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=33bff678-7829-479e-9110-b8e33a0bc0aa |
EXONDYS 51(eteplirsen)注射剂简介：近日，新药Exondys 51(eteplirsen)注射剂，成为首个获美国FDA批准治疗杜氏肌营养不良症(DMD)的药物。Exondys 51(eteplirsen)专门适用于抗肌营养不良蛋白基因(dystrophin gene)中存在确证突变可导致51号外 ... 责任编辑：admin
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