—美国FDA批准在儿童和成年患者治疗一种罕见酶疾病的第一个药物
近日，Kanuma(sebelipase alfa)获得FDA的批准为首个治疗溶酶体酸脂酶症（LAL-D）药物
药物评价和研究中心主任说：“LAL缺乏是一种罕见遗传的基因疾病可能导致严重和威胁生命器官损伤，尤其是在婴儿开始发病时” “使用这种技术，这些患者 首次获得一种治疗的机会可能改善他们的生命和生存的机会。”兽药中心CVM主任Bernadette Dunham，D.V.M.，Ph.D.说：“我们审评数据的全部确保母鸡在它们的蛋清中没有产生rhLAL，没有遭受来自引入rDNA 构建的任何不良健康影响。公司已采取严格步骤确保邻近鸡没有鸡蛋也没有进入食品供应，和我们通过检查制造设备已验证他们的围堵系统。” 孤儿药物，突破性治疗，优先审评和罕见儿童疾病优先审评凭证
批准日期：2015年12月8日；公司：Alexion Pharmaceuticals，Inc.
KANUMA(sebelipase alfa)注射液，供静脉使用
美国初次批准：2015
作用机制
LAL缺乏是一种常染色体隐性溶酶体贮积疾病特征是遗传缺陷导致溶酶体酸性脂肪酶(LAL)酶活性的明显减低或丧失。LAL酶的主要作用部位是溶酶体，在那里酶正常地致脂质颗粒包括循环LDL-胆固醇[LDL-c]分解。LAL酶活性的缺乏导致由于在多个器官，包括肝，脾，小肠，和血管壁溶酶体中胆固醇酯和甘油三酯积蓄进行性并发症。脂质在肝中蓄积的结果导致肝脂肪含量增加和肝病进展，包括纤维化和硬化，在小肠壁脂质蓄积导致吸收不良和生长衰竭。平行地，血脂异常由于溶酶体脂质降解的受损常与升高的LDL-c和甘油三酯和低HDL-胆固醇(HDL-c)。
Sebelipase α通过蛋白上表达的聚糖[glycans]结合至细胞表面受体和随后被内化至溶酶体。 Sebelipase α催化胆固醇酯和甘油三酯的溶酶体水解至游离胆固醇，甘油和游离脂肪酸。
适应证和用途
KANUMA™是一种特异性水解溶酶体胆固醇酯和甘油三酯酶适用为有溶酶体酸性脂肪酶(LAL)缺乏诊断患者的治疗。
剂量和给药方法
患者生命前6个月中呈现迅速地进展LAL缺乏：推荐的起始剂量为1mg/kg作为一个静脉输注每周1次。对没有实现最佳临床反应患者，增加至3 mg/kg每周1次。
有LAL缺乏儿童和成年患者：推荐剂量为1 mg/kg作为一个静脉输注每隔周1次。
给药指导：
⑴ 至少历时2小时输注。
⑵对3 mg/kg剂量或如发生一个超敏性反应考虑进一步延长输注时间。
⑶对1 mg/kg剂量耐受输注患者考虑1-小时输注。
剂型和规格
注射液：20mg/10mL(2mg/mL)溶液在一次性小瓶中。
禁忌证
无。
警告和注意事项
超敏性反应包括过敏反应：输注期间和后观察患者。根据反应的严重程度考虑中断输注或降低输注速率。如发生一个严重超敏性反应，立即停止输注和开始适当的治疗。用解热药和/或抗组织胺类预先治疗在那些需要对症治疗的病例中可能预防随后的反应。
对蛋或蛋产品超敏性：在有已知全身性超敏性反应对蛋或蛋产品患者考虑治疗的风险和获益。
不良反应
最常见不良反应是：
生命前6个月中呈现有迅速地进展疾病患者(≥30%)：腹泻，呕吐，发热，鼻炎，贫血，咳嗽，鼻咽炎，和荨麻疹。
儿童和成年患者(≥8%)：头痛，发热，口咽部疼痛，鼻咽炎，乏力，便秘，和恶心。
如何供应/贮存和处置
KANUMA 20 mg/10 mL小瓶以无菌，无防腐剂，无热原溶液在一次性，玻璃小瓶供应。
NDC 25682-007-01：20 mg/10 mL小瓶
KANUMA贮存在冰箱2°C至8°C(36°F至46°F)间在原始纸盒中避光保护。不要摇晃或冻结小瓶

FDA Approves Kanuma™ (sebelipase alfa) for the Treatment of Patients with Lysosomal Acid Lipase Deficiency (LAL-D)
–Kanuma is the First Approved Treatment in the United States for Patients Suffering from LAL-D, a Life-threatening and Ultra-rare Metabolic Disorder –
IMPORTANT SAFETY INFORMATION:
WARNINGS AND PRECAUTIONS
Hypersensitivity reactions, including anaphylaxis, have been reported in KANUMA-treated patients. In clinical trials, 3 of 106 (3%) patients treated with KANUMA experienced signs and symptoms consistent with anaphylaxis. These patients experienced reactions during infusion with signs and symptoms including chest discomfort, conjunctival injection, dyspnea, generalized and itchy rash, hyperemia, swelling of eyelids, rhinorrhea, severe respiratory distress, tachycardia, tachypnea, and urticaria. Anaphylaxis has occurred as early as the sixth infusion and as late as 1 year after treatment initiation.
In clinical trials, 21 of 106 (20%) KANUMA-treated patients, including 9 of 14 (64%) infants and 12 of 92 (13%) pediatric patients, 4 years and older, and adults experienced signs and symptoms either consistent with or that may be related to a hypersensitivity reaction. Signs and symptoms of hypersensitivity reactions, occurring in two or more patients, included abdominal pain, agitation, fever, chills, diarrhea, eczema, edema, hypertension, irritability, laryngeal edema, nausea, pallor, pruritus, rash, and vomiting. The majority of reactions occurred during or within 4 hours of the completion of the infusion. Patients were not routinely pre-medicated prior to infusion of KANUMA in these clinical trials.
Due to the potential for anaphylaxis, appropriate medical support should be readily available when KANUMA is administered.
Hypersensitivity to Eggs or Egg Products: Consider the risks and benefits of treatment in patients with known systemic hypersensitivity reactions to eggs or egg products.
ADVERSE REACTIONS
The most common adverse reactions are: In patients with Rapidly Progressive Disease Presenting within the First 6 Months of Life (≥30%): diarrhea, vomiting, fever, rhinitis, anemia, cough, nasopharyngitis, and urticaria. In pediatric and adult patients (≥8%): headache, fever, oropharyngeal pain, nasopharyngitis, asthenia, constipation, and nausea.
Please click here for the full Prescribing Information.
http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/125561s000lbl.pdf