VIMIZIMTM (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 VIMIZIMTM (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.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
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

FDA提前批准治疗罕见儿童疾病新药Vimizim(elosulfase alfa)
近日，Biomarin Pharmaceutical 公司的新药Vimizim(elosulfase alfa)被FDA正式批准，提前两周公布确实出人意料（原定于2月28日）。因FDA公布时间较晚，当日Biomarin 股票收盘价（75.78美元）并未受到影响。
Vimizim 是首个被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著，病人寿命多为20～30岁。目前全美约有800名Morquio A综合症患者。
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。
批准日期： 2014年2月18日；公司：BioMarin Pharmaceutical Inc.
VIMIZIM (elosulfase alfa)注射剂，为静脉使用
美国初始批准：2014
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
2 mg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。