近日，美国食品药品监督管理局(FDA)批准Vimizim(重组人 N-乙酰半乳糖胺-6-硫酸硫酸酯酶(rhGALNS) elosulfase alfa)，为粘多糖贮基症类型IVA(Morquio A综合征) 第一个FDA-批准的治疗。
Morquio A综合征是一种罕见的，常染色体隐性遗传性溶酶体贮存疾病通过N-乙酰半乳糖胺-6-硫酸硫酸酯酶(GALNS)缺乏引起。Vimizim意向取代重要代谢途径涉及的丢失GALNS酶。缺乏此酶导致骨发育，生长和移动性问题。在美国约有800例有Morquio A综合征患者。
FDA的药物评价和研究中心胃肠道和先天错误产品部副主任Andrew E. Mulberg医学博士说“这个批准和罕见儿童疾病优先审评凭证强调监管局使有罕见病患者可得到治疗的承诺，”“在批准前有这种罕见病患者没有批准的药物治疗。”
批准日期： 2014年2月14日；公司：BioMarin Pharmaceutical Inc.
VIMIZIM (elosulfase alfa)注射剂，为静脉使用
美国初始批准：2014
作用机制
粘多糖病包括糖胺聚糖(GAG)的降解代谢所需特异性溶酶体酶的缺乏引起的一组溶酶体贮存疾病。粘多糖病IVA(MPS IVA，Morquio A综合征)的特征是N-乙酰半乳糖胺-6-硫酸酯酶活性缺乏或明显减低。硫酸酯酶活性不足导致和器官功能障碍。Vimizim意向提供外源性酶N-乙酰半乳糖胺-6-硫酸酯酶将被摄取至溶酶体和增加GAGs 糖胺聚糖硫酸角质素(KS)和C6S的降解代谢。Elosulfase alfa被细胞摄取至溶酶体是通过elosulfase alfa与甘露醇-6-磷酸受体的甘露糖-6-磷酸-末端的寡糖链的结合介导的。
缺乏概括人类的疾病表型动物疾病模型，elosulfase alfa药理学活性是来自两例MPS IVA 患者人类原代软骨细胞评价的。MPS IVA软骨细胞用elosulfase alfa治疗诱发从软骨细胞糖胺聚糖硫酸角质素(KS)溶酶体贮存清除。
适应证和用途
Vimizimis一种水解溶酶体糖胺聚糖(GAG)-特异性酶适用为患者有粘多糖病型IVA(MPS IVA；Morquio A综合征)。
剂量和给药方法
2mg每公斤体重给予每周1次作为一次根据输注容积历时最小3.5至4.5小时静脉输注。
剂型和规格
注射剂：5mg/5mL(1mg/mL)在单次使用小瓶内。
禁忌证
无。
警告和注意事项
（1）过敏反应和超敏性反应：有些患者用Vimizim治疗期间曾观察到危及生命过敏反应和超敏性反应。如发生过敏反应或严重超敏性反应，立即停止输注和开始适当医学治疗。建议开始输注前用抗组织胺有或无退热药预先治疗。
（2）急性呼吸并发症的风险：有急性发热或呼吸疾病患者可能处在来自超敏性反应危及生命并发症高危风险。给予Vimizim前应对患者的临床状态给予仔细考虑和考虑延迟Vimizim输注。
不良反应
最常见不良反应(Vimizim患者≥10%和发生比安慰剂-治疗患者发生率较高)是发热，呕吐，头痛，恶心，腹痛，畏寒，和乏力。
特殊人群中使用
儿童使用：在小于5岁儿童患者中尚未确定Vimizim的安全性和有效性。
包装供应/贮存和处置
Vimizim以一种浓缩溶液为输注(1mg每mL)供应需要稀释。一小瓶5mL含5mg Vimizim。
NDC 68135-100-01，5mL小瓶。
贮存Vimizim在冰箱2°C至8°C(36°F至46°F)，不要冻结或摇晃。避光保护。
已稀释Vimizim应立即使用。如不可能立即使用，已稀释的Vimizim可贮存在2°C至8°C (36°F至46°F)至24小时随后给药期间长达24小时在23°C至27°C (73°F至81°F)。
完整说明书附件：
https://www.vimizim.com/v22018/wp-content/uploads/2018/02/Prescribing-Information.pdf
VIMIZIM® (elosulfase alfa) is indicated for patients with Mucopolysaccharidosis type IVA (MPS IVA; Morquio A syndrome).
Important Safety Information
Life-threatening allergic reactions, known as anaphylaxis, can occur during VIMIZIM® (elosulfase alfa) infusions. Typical signs of anaphylaxis include cough, rash, throat tightness, hives, flushing, changes in skin color, low blood pressure, shortness of breath, chest pain, and gastrointestinal symptoms such as nausea, abdominal pain, retching, and vomiting. Contact your doctor or get medical help right away if these symptoms occur during or after VIMIZIM infusions. If you have a respiratory illness, you may be at risk for a sudden worsening of your condition, and you may require additional monitoring.
VIMIZIM is a prescription medicine. Before treatment with VIMIZIM, it is important to discuss your medical history with your doctor. Tell your doctor if you are sick or taking any medication and if you are allergic to any medicines. Also tell your doctor if you are pregnant, planning to become pregnant, or are a nursing mother. Your doctor will decide if VIMIZIM is right for you. If you have questions or would like more information about VIMIZIM, contact your doctor.
Anaphylaxis can occur during any VIMIZIM infusion and up to three hours after any infusion, and hypersensitivity reactions have been observed as early as 30 minutes from the start of infusion but as late as six days after infusion.
Serious and severe reactions can happen with VIMIZIM treatment, including life-threatening allergic reactions (anaphylaxis), hives, swelling, cough, shortness of breath, and flushing. You should receive medication such as antihistamines before VIMIZIM infusions to reduce the risk of reactions. If a reaction occurs, the infusion should be slowed or stopped and you may be given additional medication. If a severe reaction occurs, the infusion should be stopped immediately and you will receive appropriate medical treatment.
If you have acute febrile or respiratory illness at the time of VIMIZIM infusion you may be at higher risk of life-threatening complications from hypersensitivity reactions. If you use supplemental oxygen or continuous positive airway pressure (CPAP) you should have it available during your infusion in the event of a sudden reaction, or extreme drowsiness/sleep from antihistamines.
Spinal cord damage may occur due to the natural MPS IVA disease process. Signs of spinal cord injury include back pain, numbness and paralysis, and loss of bladder and bowel control. Contact your doctor immediately if you develop any of these symptoms.
The most common side effects reported during VIMIZIM infusions included fever, vomiting, headache, nausea, abdominal pain, chills, and fatigue. These are not all of the possible side effects with VIMIZIM. Talk to your doctor if you have any symptoms that bother you or that do not go away.