近日，美国FDA批准Strensiq（asfotase alfa）作为首款获得批准的治疗药物用于围产期、婴儿及幼儿期发作的低磷酸酯酶症（HPP）。 低磷酸酯酶症是一种罕见的、遗传性、进展性代谢疾病，该病患者的多个人体系统会经历灾难性的影响，导致严重残疾及危及生命的并发症。该疾病的特征是有缺陷的骨骼矿物化，这可导致佝偻病及导致骨骼畸形的骨软化。 低磷酸酯酶症也能引起并发症，如失去运动能力的重度肌无力、癫痫发作、疼痛、呼吸衰竭和过早死亡。严重形式的低磷酸酯酶症影响了大约十万之一的新生儿，但轻微病例，如在儿童或成年期出现的低磷酸酯酶症可能发生的更频繁一些。 FDA的药品评价和研究中心中药物评价III室副主任说：“这是首次，HPP社会经得到一种被对这种罕见病的批准治疗，” “Strensiq的批准是一个实例表明突破性治疗指定程序如何能为有罕见病人们带来新和需要的治疗。”突破性治疗指定，孤儿药物指定，优先审评，罕见儿童疾病优先审评凭证。 Strensiq通过注射给药，每周注射三次或六次。Strensiq通过替代在正常骨骼中负责一种主要矿物质形成的酶（称组织非特异性碱性磷酸酶）而发挥作用，这种酶已显示能改善患者的结局。 Strensiq的安全性与有效性在 99 名围产期（疾病在子宫时发生，出生时比较明显）、婴儿期或幼儿期发作的低磷酸酯酶症患者中得到证实，这些患者在四项前瞻性、开放式研究中接受该药物治疗长达6.5年时间。 批准日期: 2015年10月23日；公司: Alexion Pharmaceuticals公司 STRENSIQ（asfotase alfa）注射液，为皮下使用 美国首次批准：2015年 近期主要变化 警告和注意事项：10/2016 作用机制 HPP由TNSALP酶活性的缺乏引起，其导致几种TNSALP底物（包括无机焦磷酸（PPi））的升高。 提高的细胞外水平的PPi阻断羟基磷灰石晶体生长，抑制骨矿化并导致未矿化的骨基质的积累，其显示为婴儿和儿童的r ets病和骨变形，以及一旦生长板闭合时的骨软化（软骨化）以及肌肉无力。 在STRENSIQ处理时替换TNSALP酶降低酶底物水平。 适应症和用法 STRENSIQ®是一种组织非特异性碱性磷酸酶，用于治疗围产期/婴儿和幼年型低磷酸酯症（HPP）患者。 剂量和给药 围产期/婴儿发病HPP 推荐的剂量方案是每周三次皮下施用2mg/kg，或者每周施用6mg/kg的1mg/kg。注射部位反应可能限制每周6次方案的耐受性。 剂量可以增加至3mg/kg，每周三次，因为功效不足。 少年发作HPP 推荐的剂量方案是每周三次皮下施用2mg/kg，或者每周施用6mg/kg的1mg/kg。注射部位反应可能限制每周6次方案的耐受性。 制备和基于重量的给药： 注意：不要在体重小于40kg的儿科患者中使用80mg/0.8mL小瓶，因为80mg/0.8 mL小瓶（更高浓度）实现的全身性asfotase alfa暴露低于其他强度小瓶实现的较低浓度）。较低的暴露可能不足以用于这个亚组患者。 请参阅治疗方案基于体重的给药表的完整处方信息。 行政： 仅用于皮下注射。 旋转注射部位。不要给予发红，发炎或肿胀的部位。 剂量形式和强度 注射：一次性使用小瓶中的18mg/0.45mL，28mg/0.7mL，40mg/mL或80mg/0.8mL溶液。 禁忌症 没有。 警告和注意事项 超敏反应：监测并且如果发生严重反应，停止治疗并开始适当的治疗。 脂肪营养不良：在治疗几个月后报告局部反应;遵循适当的注射技术和旋转注射部位。 异位钙化（眼和肾）：在基线时和在治疗期间定期地使用眼科检查和肾超声监测。 不良反应 最常见的不良反应（≥10％）是注射部位反应，脂肪营养不良，异位钙化和超敏反应。 STRENSIQ (asfotase alfa) solution for subcutaneous injection Strensiq® Strensiq® (asfotase alfa) is an innovative enzyme replacement therapy approved in the United States for the treatment of patients with perinatal/infantile-and juvenile-onset hypophosphatasia (HPP).Strensiq is also approved in the European Union, Japan and Canada. About HPP HPP is a genetic, chronic, progressive and life-threatening metabolic disease in which patients experience devastating effects on multiple systems of the body, leading to debilitating or life-threatening complications. HPP is characterized by low alkaline phosphatase (ALP) activity and defective bone mineralization that can lead to destruction and deformity of bones and other skeletal abnormalities, as well as systemic complications such as muscle weakness and respiratory failure leading to premature death in infants. HPP is caused by a defect (mutation) in the gene that makes an enzyme known as tissue non-specific alkaline phosphatase (TNSALP), resulting in low levels of ALP activity. When ALP is functioning normally, it allows two key minerals – calcium and phosphate–to bind together to form healthy, mineralized bones. In patients with HPP, however, ALP activity is low, leading to insufficient mineralization of bone and altered calcium and phosphate metabolism. Many patients with HPP have weak, soft, or brittle bones, as well as skeletal deformities including HPP-related rickets and bowed legs. These abnormalities can impede growth in children and can continue to impair a person’s mobility. Infants and young children may experience severe symptoms of HPP, such as respiratory failure, that can lead to premature death, or severe breathing complications that require an assistive breathing device. In a retrospective natural history study of children with severe HPP, those who experienced their first symptom of HPP prior to six months of age had a very high mortality rate—73% at five years. Treating Patients Who Have HPP with Strensiq Strensiq is the first therapy to treat the underlying cause of HPP—deficient ALP. By replacing the deficient ALP, Strensiq reduces the elevated enzyme substrate levels and improves bone mineralization. Strensiq is administered via subcutaneous injection (injection under the skin). In clinical trials, patients with perinatal/infantile-onset HPP who were treated with Strensiq had a significant improvement in survival compared with untreated historical control patients. At 48 weeks, estimated survival was 97% for Strensiq-treated patients compared with 42% for historical control patients (Hazard Ratio [95% CI]: 0.14 [0.05, 0.39]). Patients treated with Strensiq also demonstrated significant radiographic improvement. In patients with perinatal/infantile-onset HPP, 74% (50/68) of Strensiq-treated patients were rated as responders on the 7-point Radiographic Global Impression of Change (RGI-C) scale at last assessment (mean 24 months). In patients with juvenile-onset HPP, 100% of Strensiq-treated patients (8/8) were rated as RGI-C responders by 54 months of treatment compared with 6% (2/32) of untreated historical control patients. The most common adverse reactions (≥10%) are injection site reactions, lipodystrophy, ectopic calcification, and hypersensitivity reactions. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3387574f-5eaa-4501-a71d-4cbfbd563031