近日，BiomarinPharmace-utical公司的新药Vimizim（elosulfasealfa）获FDA正式批准，Vimizim是首只被FDA批准的治疗粘多糖沉积症IVA型的药物。粘多糖病Ⅳ型（Morquio氏病）有两个亚型。其病因为ⅣA为半乳糖-6-硫酸酯酶（GALNS）缺乏，ⅣB为β-D半乳糖酶缺乏。该病为常染色体隐性遗传，其临床特点为明显的生长迟缓，步态异常和骨骼畸形且逐渐显着，病人寿命多为20～30岁。目前全美约有800名MorquioA综合征患者。
Vimizim能够替代患者体内缺乏的GALNS酶。通过176位病人的临床试验证实了该药物的安全性和有效性。依据FDA报告，其最常见的副作用包括发烧、头痛、恶心、腹痛和疲劳。
VIMIZIM Rx
Pharmacological Class:
Hydrolytic lysosomal glycosaminoglycan (GAG)-specific enzyme.
Active Ingredient(s):
Elosulfase alfa 1mg/mL; soln for IV infusion; preservative-free.
Company
BioMarin Pharmaceuticals
Indication(s):
Mucopolysaccharidosis type IVA (MPS IVA; Morquio A syndrome).
Pharmacology:
Vimizim is intended to provide the exogenous enzyme N-acetylgalactosamine-6-sulfatase that will be taken up into the lysosomes and increase the catabolism of the glycosaminoglycans KS and C6S. Elosulfase alfa uptake by cells into lysosomes is mediated by the binding of mannose-6-phosphate-terminated oligosaccharide chains of elosulfase alfa to mannose-6-phosphate receptors.
Clinical Trials:
The safety and efficacy of Vimizim were assessed in a 24-week, randomized, double-blind, placebo-controlled clinical trial involving 176 patients with MPS IVA. The majority of the patients (82%) presented with a medical history of musculoskeletal conditions, which includes knee deformity (52%), kyphosis (31%), hip dysplasia (22%), prior spinal fusion surgery (22%) and arthralgia (20%). At baseline, all enrolled patients could walk more than 30 meters (m) but less than 325m in 6 minutes.
Patients received Vimizim 2mg/kg once per week (n=58), Vimizim 2mg/kg once every other week (n=59), or placebo (n=59). The primary endpoint was the change from baseline in the distance walked in six minutes (6-minute walk test, 6-MWT) at Week 24. The other endpoints included changes from baseline in the rate of stair climbing in three minutes (3-minute stair climb test, 3-MSCT) and changes from baseline in urine KS levels at Week 24.
The treatment effect in the distance walked in 6 minutes, compared to placebo, was 22.5m (95% CI: 4.0, 40.9; P=0.0174) in patients who received Vimizim 2mg/kg once per week. There was no difference in the rate of stair climbing between patients who received Vimizim 2mg/kg once per week and those who received placebo. Patients who received Vimizim 2mg/kg once every other week performed similarly in the 6-MWT and 3-MSCT as those who received placebo. The reduction in urinary KS levels from baseline, a measure of pharmacodynamic effect, was greater in the Vimizim treatment groups compared to placebo. The relationship between urinary KS and other measures of clinical response has not been established.
Legal Classification:
Rx
Adults & Children:
<5 years: not established. Give by IV infusion over 3.5–4.5 hours based on infusion volume. ≥5 years: 2mg/kg once weekly. Pre-treat with antihistamines with or without antipyretics 30–60 mins prior to infusion.
Warnings/Precautions:
Risk of serious anaphylactic reactions; observe patients during and after administration. Have epinephrine inj available. Discontinue immediately if severe hypersensitivity reactions occur. Acute febrile or respiratory illness; evaluate clinical status prior to therapy and consider delaying infusion. Risk of sleep apnea; consider evaluating airway patency prior to initiation. Have supplemental oxygen or continuous positive airway pressure available. Monitor for signs/symptoms of spinal or cervical cord compression. Pregnancy (Category C). Nursing mothers.
Adverse Reaction(s)
Pyrexia, vomiting, headache, nausea, abdominal pain, chills, fatigue; sleep apnea, anaphylaxis, possible antibody formation.
Notes:
To enroll in the Morquio A Registry for monitoring effects of Vimizim contact MARS@bmrn.com or call (800) 983-4587.
How Supplied:
Single-use vial (5mL)—1
LAST UPDATED:
4/3/2014
美国FDA批准首个IVA型粘多糖贮积病治疗药
2014年2月14日，美国FDA批准Vimizim (elosulfase alfa)上市，这是FDA批准的首款粘多糖贮积症IVA型（Morquio综合征A型）治疗药物。
粘多糖贮积症IVA型是一种罕见的、常染色体隐性遗传性溶酶体贮积病，由N-乙酰半乳糖胺-6-硫酸酯酶(GALNS)缺乏引起。Vimizim旨在替代该酶的功能。GALNS的缺失可导致骨生长发育问题。在美国大约有800名Morquio综合征A型患者。
Vimizim被授予了优先审评权。FDA优先审评权为严重疾病或病症治疗可能提供重要改善的药物提供了一种加快的审评途径。Vimizim也是首款获得罕见儿科疾病优先评审权的药物，罕见儿科疾病优先评审权旨在鼓励用于罕见儿科疾病预防和治疗的新药和生物制剂开发的一个条款。
“这次的批准及罕见儿科疾病优先评审权凸显了FDA让罕见病患者获得治疗药物的承诺，”FDA药物评价与研究中心(CDER) 胃肠病学和先天缺陷产品部门副主任、医学博士Andrew E. Mulberg说。
Vimizim的安全性和有效性基于一项由176名Morquio综合征A型患者参与的临床试验，患者年龄从5岁到57岁不等。经由Vimizim治疗的受试者在6分钟行走试验中，与安慰剂治疗患者相比显示出更大的改善。临床试验显示，Vimizim用药患者6分钟行走与安慰剂治疗患者相比平均多走22.5米。
临床试验期间，Vimizim最常见的副作用有发热、呕吐、头痛、恶心、腹痛、寒战和疲劳。Vimizim对5岁以下儿科患者的安全性和有效性尚未确定。Vimizim获得批准时带有一项黑框警告，提示有过敏性风险。临床试验期间，危及生命的过敏反应在一些患者输注Vimizim时发生。
Vimizim由加利福尼亚州诺瓦托的BioMarin制药公司上市销售。