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FDA批准Exondys 51注射液用于治疗杜氏肌营养不良症

2016-09-22 06:25:52 作者：新特药房来源：互联网浏览次数：0 文字大小：【大】【中】【小】

简介： 新药Exondys 51(eteplirsen)注射液获美国FDA批准为杜氏肌营养不良症的第一个药物2016年9月19日美国食品和药品监管局(FDA)批准Exondys_51(eteplirsen)注射液，被批准治疗有杜氏肌营养不良症(DMD)患者第一个 ...

关键字：eteplirsen商品名exondys_51注射液杜氏肌营养不良突破治疗孤儿药物加速批准快速通道

——新药Exondys 51(eteplirsen)注射液获美国FDA批准为杜氏肌营养不良症的第一个药物
2016年9月19日美国食品和药品监管局(FDA)批准Exondys_51(eteplirsen)注射液，被批准治疗有杜氏肌营养不良症(DMD)患者第一个药物。Exondys 51是一种特异性地适用为患者有一种肌营养不良蛋白[dystrophin]基因的确证的突变对外显子51跳针[skipping]负责，这影响约13% DMD人群。
FDA的药物评价和研究中心主任Janet Woodcock，M.D说：“有一种杜氏肌营养不良症的特殊类型患者现将取得对这种罕见和灾难性谢疾病被批准治疗，”“在罕见病中，由于被每种病受影响的人数少和许多疾病的医学了解缺乏是特殊地挑战。加速批准使得患者根据初始数据这种药物，但通过公司必须在批准后进行一个验证性临床试验我们热切期待着更多地了解这种药物的疗效。”
DMD是一种罕见遗传疾病特征是渐进性肌肉退化和衰弱。它是肌营养不良症的最常见类型。DMD是被肌营养不良蛋白的一种缺乏引起的，这是一种蛋白帮助肌肉细胞完整。通常在三和五岁间见到第一个症状，而随时间恶化。这种疾病经常发生在没有情况和原发影响男孩已知的家族史人们，但在罕见病例它可能影响女孩。世界范围DMD发生在约为每3,600男性婴儿一个。
有DMD人们逐渐地丧失独立地进行活动的能力和经常在他们十几岁需要使用轮椅。随着病情的进展，可能发生危及生命心脏和呼吸情况。患者典型地屈从于这种疾病在20多岁或30多；但是，疾病严重程度和严重程度变化。
Exondys 51在加速批准途径下被批准，它对提供对治疗严重或危及生命疾病和一般地提供一个超过已存在治疗有意义优点获益的批准药物。在这个途径下批准可能根据适当和对照良好研究显示该药物对某个合理地可能预测对患者临床获益(一位患者如何感觉或功能或是否他们活存)替代性终点有某种影响。这个通路提供患者较早得到鼓舞人有前途新药同时公司进行临床试验证明这个预测的临床获益。
Exondys 51的加速批准是根据替代性终点在有些Exondys 51-被治疗患者观察到在骨骼肌中肌营养不良蛋白增加。FDA已得出结论申请者递交的数据显示肌营养不良蛋白生成中某种增加是合理地可能预测在有DMD有些患者临床获益对外显子51跳针[skipping]负责肌营养不良蛋白基因。尚未确定Exondys 51的临床获益，包括改善运动功能。在做出这个决定中， FDA考虑伴随这个药物的潜在风险，疾病对这些儿童危及生命和这个疾病灾难性性质和缺乏可得到的治疗。
在加速批准条款下，FDA正在要求Sarepta Therapeutics公司进行一项临床试验确证药物的临床获益。这个被要求研究被设计成评估Exondys 51是否改善确证对外显子51跳针[skipping]负责肌营养不良蛋白基因的DMD患者的运动功能。如果这项试验证明临床获益失败，FDA可能开始撤销批准该药的法律程序。
在临床试验用Exondys 51参加者报告的最常见副作用是平衡障碍和呕吐。
FDA赋予Exondys 51快速通道指定，这是一种指定以加速是意向治疗严重情况和显示面对某种未满足医疗需求药物的发展和促进审评。它还赋予优先审评和孤儿药物指定。优先审评状态是赋予对，如被批准，将是显著改善某种严重情况的治疗中安全性和有效性药物申请。孤儿药物指定提供奖励例如临床试验税收减免，用户费用减免和对孤儿药物专营权合格性以帮助和鼓励对罕见病药物的开发。
制造商接受一个罕见儿童疾病优先审评凭证，这来自一个程序意向鼓励为预防和治疗罕见儿童疾病的药和生物制品的发展。这是自从程序开始的发出的第七个罕见儿童疾病优先审评凭证。
Exondys 51是由麻省剑桥Sarepta Therapeutics公司制造。
杜氏肌营养不良症
DMD是一种比较罕见的X染色体隐性遗传疾病，特点是进行性肌肉退化和萎缩，它是肌营养不良的最常见的类型。由于编码抗肌萎缩蛋白基因（dystrophin）突变，DMD患者很少或没有这个涉及到肌纤维功能的重要蛋白，于是肌肉细胞不能保持完整结构。
据统计，全球平均每3600个新生男婴中就有一人罹患此疾病。患者在儿童期就会因骨骼肌不断退化出现肌肉无力或萎缩，导致行走不便。
症状通常早在三五岁之时就会出现，并且逐渐恶化；大概在十几岁时，会彻底丧失行走能力，需要使用轮椅。通常到20～30多岁，病人就会发生威胁生命的心脏和呼吸系统疾病而死亡。目前尚无任何用以治疗该病的上市药物。
EXONDYS 51 the first DMD treatment approved in the US, targets dystrophin deficiency, the underlying cause of Duchenne
U.S. Food and Drug Administration (FDA) has granted accelerated approval for EXONDYS 51 (eteplirsen) as a once weekly intravenous infusion of 30 milligrams per kilogram for the treatment of Duchenne muscular dystrophy (DMD) in patients who have a confirmed mutation in the DMD gene that is amenable to exon 51 skipping. This indication is based on an increase in dystrophin in skeletal muscles 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 trials.
The most common adverse reactions compared to a placebo group were vomiting (38%) and balance disorder (38%) with contusion, excoriation, arthralgia, rash, catheter site pain, and upper respiratory tract infection also reported more frequently than placebo (≥ 10%).
“Today’s accelerated approval of EXONDYS 51 represents a major milestone in the treatment of Duchenne Muscular Dystrophy for patients amenable to skipping exon 51 by targeting the underlying genetic cause of the disease–the lack of the dystrophin protein,” said Edward Kaye, M.D., Sarepta’s interim chief executive officer and chief medical officer.
“We are grateful to the many patients and investigators who participated in EXONDYS 51’s clinical studies.
EXONDYS 51 represents the culmination of many years of work across our entire organization and the Duchenne community to address a critical unmet need by bringing this novel medicine to patients.
We will continue to leverage what we have learned from EXONDYS 51 to facilitate future development of potential new treatments targeting additional exons with the goal of one day treating all DMD patients amenable to exon skipping.”
The underlying cause of Duchenne muscular dystrophy is a mutation or error in the gene for dystrophin, an essential protein involved in muscle fiber function.
Certain genetic mutations in DMD involve the deletion of exons, which interrupt proper translation of the genetic code into protein.
Duchenne muscular dystrophy is a fatal genetic neuromuscular disorder affecting an estimated one in approximately every 3,500 – 5,000 males born worldwide. It is estimated that up to thirteen percent of people with DMD have mutations addressable by
About Duchenne Muscular Dystrophy (DMD)
DMD is an X-linked rare degenerative neuromuscular disorder causing severe progressive muscle loss and premature death.
DMD is estimated to affect approximately one in every 3,500-5000 males born worldwide.
A devastating and incurable muscle-wasting disease, DMD is associated with specific errors in the gene that codes for dystrophin, a protein that plays a key structural role in muscle fiber function. Progressive muscle weakness in the lower limbs spreads to the arms, neck and other areas.
Eventually, increasing difficulty in breathing due to respiratory muscle dysfunction requires ventilation support, and cardiac dysfunction can lead to heart failure. The condition is universally fatal, and death usually occurs before the age of 30.
com.
About EXONDYS 51
EXONDYS 51 uses Sarepta’s proprietary phosphorodiamidate morpholino oligomer (PMO) chemistry and exon-skipping technology to skip exon 51 of the dystrophin gene. EXONDYS 51 is designed to bind to exon 51 of dystrophin pre-mRNA, resulting 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.
Data from clinical studies of EXONDYS 51 in a small number of DMD patients have demonstrated a consistent safety and tolerability profile.
The pivotal trials were not designed to evaluate long-term safety and a clinical benefit of EXONDYS 51 has not been established.
Important Safety Information
Adverse reactions observed in patients (N=8) treated with 30 or 50 mg/kg/wk of EXONDYS 51 with incidence ≥ 25% and higher than in the placebo group (N=4) (Study 1) were: balance disorder (38%), vomiting (38%) and contact dermatitis (25%).
The most common adverse reactions were balance disorder and vomiting.
?The following events were reported in ≥10% of patients treated with EXONDYS 51 for up to 208 weeks (N=88) and occurred more frequently than placebo in a controlled trial for 24 weeks (Study 1): vomiting, contusion, excoriation, arthralgia, rash, catheter site pain, and upper respiratory tract infection.
?There have been reports of transient erythema, facial flushing, and elevated temperature occurring on the day of EXONDYS 51 infusion.
http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/206488lbl.pdf