近日，美国食品药品监督管理局（FDA）已批准的Vyondys 53（Golodirsen）上市。Vyondys 53是一种来自Sarepta的磷酸二酰胺基吗啉代寡聚物（PMO）平台的反义寡核苷酸，适用于已确诊易发生外显子53突变的患者的杜氏肌营养不良症（DMD）的治疗。
批准日期：2019年12月12日  公司：Sarepta Therapeutics，Inc.
VYONDYS 53（golodirsen）注射液，用于静脉内使用
美国初次批准：2019
作用机理
Golodirsen被设计为与肌营养不良蛋白前体mRNA的第53外显子结合，从而导致在具有易发生第53外显子跳跃的遗传突变的患者的mRNA加工过程中将此exon排除在外。 外显子53跳跃的目的是在具有适合外显子53跳跃的遗传突变的患者中产生内部截短的肌营养不良蛋白[见临床研究]。
适应症和年龄
VYONDYS 53是一种反义寡核苷酸，适用于患有Duchenne肌营养不良症（DMD）的患者，这些患者已确诊了DMD基因突变，适合外显子53跳过。根据VYONDYS 53治疗的患者骨骼肌中肌营养不良蛋白产量的增加，该适应症在加速批准下获得批准。对该适应症的持续批准可能取决于在验证试验中对临床益处的验证。
剂量和给药
•开始前测量肾小球滤过率。
•每周一次，每公斤30毫克。
•在35至60分钟内静脉输注。
•给药前需要稀释。
剂量形式和强度
注射剂：单剂量小瓶中100mg/2mL（50mg/mL）。
禁忌症
没有
警告和注意事项
•超敏反应：接受VYONDYS 53治疗的患者发生超敏反应，包括皮疹，发热，瘙痒，荨麻疹，皮炎和皮肤脱落。如果发生超敏反应，请采取适当的医疗措施，并考虑减慢输注速度或中断VYONDYS 53疗法。
•肾脏毒性：根据动物数据，可能会引起肾脏毒性。应监测肾功能；肌酐可能不是DMD患者肾功能的可靠指标。
不良反应
最常见的不良反应（发生率≥20％，高于安慰剂）为头痛，发热，跌倒，腹痛，鼻咽炎，咳嗽，呕吐和恶心。
包装供应/存储和处理方式
供应方式
VYONDYS 53注射液以单剂量瓶提供。 该溶液为澄清至微乳白色的无色液体。
•含有100mg/2mL（50mg/mL）NDC的单剂量小瓶60923-465-02
储存和处理
将VYONDYS 53存放在2°C至8°C（36°F至46°F）下。 不要冻结。 存放在原始纸箱中，直到准备使用以避光。
完整说明资料附件：
https://www.vyondys53.com/Vyondys53_(golodirsen)_Prescribing_Information.pdf
U.S. Food and Drug Administration(FDA)has approved Vyondys 53™(golodirsen).Vyondys 53 is an antisense oligonucleotide from Sarepta’s phosphorodiamidate morpholino oligomer(PMO)platform, indicated for the treatment of Duchenne muscular dystrophy(DMD)in patients with a confirmed mutation amenable to exon 53 skipping. This indication is based on a statistically significant increase in dystrophin production in skeletal muscle observed in patients treated with Vyondys 53, which is reasonably likely to predict clinical benefit for those patients who are exon 53 amenable.
About Vyondys 53
Vyondys 53 is an antisense oligonucleotide indicated for the treatment of Duchenne muscular dystrophy in patients who have a confirmed mutation of the DMD gene that is amenable to exon 53 skipping. Vyondys 53 uses Sarepta’s proprietary phosphorodiamidate morpholino oligomer(PMO)chemistry and exon-skipping technology to bind to exon 53 of dystrophin pre-mRNA, resulting in exclusion, or “skipping,” of this exon during mRNA processing in patients with genetic mutations that are amenable to exon 53 skipping. Exon skipping is intended to allow for production of an internally truncated dystrophin protein.
Vyondys 53 is approved under accelerated review based on an increase in dystrophin production in skeletal muscle of patients amenable to exon 53 skipping. Continued approval may be contingent upon verification of a clinical benefit in confirmatory trials.
Vyondys 53 has met the full statutory standards for safety and effectiveness and as such is not considered investigational or experimental.
Important Safety Information for Vyondys 53
Hypersensitivity reactions, including rash, pyrexia, pruritus, urticaria, dermatitis, and skin exfoliation have occurred in Vyondys 53-treated patients, some requiring treatment.If a hypersensitivity reaction occurs, institute appropriate medical treatment and consider slowing the infusion or interrupting the Vyondys 53 therapy.
Renal toxicity was observed in animals who received golodirsen. Although renal toxicity was not observed in the clinical studies with Vyondys 53, renal toxicity, including potentially fatal glomerulonephritis, has been observed after administration of some antisense oligonucleotides. Renal function should be monitored in patients taking Vyondys 53. Because of the effect of reduced skeletal muscle mass on creatinine measurements, creatinine may not be a reliable measure of renal function in DMD patients. Measurement of glomerular filtration rate (GFR) by 24-hour urine collection prior to initiation of therapy is recommended. Monthly monitoring for proteinuria by dipstick urinalysis and monitoring of serum cystatin C every three months is recommended. In the case of a confirmed dipstick proteinuria of 2+ or greater or elevated serum cystatin C, a 24-hour urine collection to quantify proteinuria and assess GFR should be performed.
Adverse reactions observed in at least 20% of treated patients and greater than placebo were (Vyondys 53, placebo): headache (41%, 10%), pyrexia (41%, 14%), fall (29%, 19%), abdominal pain (27%, 10%), nasopharyngitis(27%, 14%), cough(27%, 19%), vomiting(27%, 19%), and nausea(20%, 10%).
Other adverse reactions that occurred at a frequency greater than 5% of Vyondys 53-treated patients and at a greater frequency than placebo were administration site pain, back pain, pain, diarrhea, dizziness, ligament sprain, contusion, influenza, oropharyngeal pain, rhinitis, skin abrasion, ear infection, seasonal allergy, tachycardia, catheter site related reaction, constipation, and fracture.