近日，FDA批准Mepsevii（vestronidase alfa-vjbk）用于儿童和成人遗传性代谢疾病-粘多糖病VII型（MPSVII）的治疗，该酶替代疗法由专注于罕见病治疗的生物制药公司Ultragenyx Pharmaceutical开发完成，此次获批也是Ultragenyx首个经过FDA批准的治疗方案。

批准日期：2017年11月15日 公司：Ultragenyx Pharmaceutical

MEPSEVII TM（vestronidase alfa - vjbk）注射液，用于静脉注射

美国最初批准：2017年

警告：

ANAPHYLAXIS查看完整的盒装警告的完整处方信息。 MEPSEVII给药时出现过敏反应，早在第一次给药时，因此在给予MEPSEVII时应该可以获得适当的医疗支持。

在MEPSEVII输注期间和60分钟后密切观察患者。

如果患者出现过敏反应，立即停止输注MEPSEVII。

作用机制

粘多糖贮积症VII（MPS VII或Sly综合征）是一种溶酶体病症，其特征在于GUS缺乏导致GAG在整个身体的细胞中积累，导致多系统组织和器官损伤。

Vestronidase alfa-vjbk是人GUS的重组形式，旨在提供外源GUS酶以摄入细胞溶酶体。 寡糖链上的甘露糖-6-磷酸（M6P）残基允许酶与细胞表面受体结合，导致酶的细胞摄取，靶向溶酶体并随后在受影响的组织中积累GAG的分解代谢。

适应症和用法

MEPSEVII是一种重组人溶酶体β葡糖醛酸酶，在儿科和成人患者中表示用于治疗粘多糖贮积症VII（MPS VII，Sly综合征）。

使用限制

MEPSEVII对MPS VII中枢神经系统表现的影响尚未确定。

剂量和给药

推荐剂量为每两周施用4mg/kg作为静脉内输注。

建议在输注开始前30至60分钟使用非镇静性抗组胺药（含或不伴有退热药）进行术前用药。

在约4小时内进行输液。在输注的第一个小时内，注入总量的2.5％。在第一个小时之后，可以增加速率以在容许的3小时内注入剩余的体积。有关剂量和体重输注速率的完整处方信息，请参见表1。

有关准备，管理和存储的其他信息，请参阅完整的处方信息。

剂量形式和强度

注射：在单剂量小瓶中10mg/5mL（2mg/mL）。

禁忌症

没有

不良反应

最常见的不良反应（≥1名患者）是：输液部位外渗，腹泻，皮疹，过敏反应，输液部位肿胀，外周肿胀和瘙痒。

如何提供/存储和处理

MEPSEVII（vestronidase alfa-vjbk）注射剂是无色至微黄色液体，以包含一个10mg/5mL（2mg/mL）单剂量小瓶（NDC 69794-001-01）的纸盒供应。

在2°C至8°C（36°F至46°F）的冷藏条件下储存。 不要冻结或摇晃。 避光。

https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=925d4e21-fd98-474d-a34d-a0b3558ed750

MEPSEVII™ (vestronidase alfa-vjbk) should be administered under the supervision of a health care professional with the capability to manage anaphylaxis

MEPSEVII is a recombinant human lysosomal beta glucuronidase indicated in pediatric and adult patients for the treatment of Mucopolysaccharidosis VII (MPS VII, Sly syndrome).

Limitations of Use 

The effect of MEPSEVII on the central nervous system manifestations of MPS VII has not been determined.

BOXED WARNING AND ADDITIONAL IMPORTANT SAFETY INFORMATION

 WARNING: ANAPHYLAXIS

•Anaphylaxis has occurred with MEPSEVII administration, as early as the first dose, therefore appropriate medical support should be readily available when MEPSEVII is administered. 

•Closely observe patients during and for 60 minutes after MEPSEVII infusion.

•Immediately discontinue the MEPSEVII infusion if the patient experiences anaphylaxis.

•Anaphylaxis to MEPSEVII was reported in 2 of 20 patients in the clinical program. The two patients with anaphylaxis to MEPSEVII during the clinical trials had one occurrence each and tolerated subsequent infusions of MEPSEVII, without recurrence. 

•Consider the risks and benefits of re-administering MEPSEVII following anaphylaxis.

•Manifestations included respiratory distress, cyanosis, decreased oxygen saturation, and hypotension. 

•Prior to discharge, inform patients of the signs and symptoms of anaphylaxis and instruct them to seek immediate medical care if symptoms occur. 

Adverse Reactions

•In a clinical trial, the most common adverse reactions occurring with MEPSEVII treatment included infusion site extravasation, diarrhea, rash, anaphylaxis, infusion site swelling, peripheral swelling, and pruritus.

•One patient experienced a febrile convulsion during MEPSEVII treatment. The patient subsequently was re-challenged without recurrence and continued on treatment. 

Use in Specific Populations

•There are no available data on MEPSEVII use in pregnant women to determine a drug-associated risk of adverse developmental outcomes. 

•There are no data on the presence of MEPSEVII in either human or animal milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for MEPSEVII and any potential adverse effects on the breastfed infant from MEPSEVII or from the underlying maternal condition.