2015年10月23日，美国食品和药品监管局FDA批准Strensiq(asfotase α)作为第一个为围产期，婴儿和青少年发病的低磷酸酯酶症(HPP)的治疗。 HPP是一种罕见的，遗传性，进展性，代谢病其中患者经受机体多系统的破坏性效应，导致严重失能残疾和危及生命合并症。其特征为缺陷性骨矿物质化可导致佝偻病和骨软化导致骨骼异常。它可能致合并症例如深度肌肉软弱运动失能，癫痫发作，疼痛，呼吸衰竭和早产死亡。HPP的严重形式影响估计在100,000新生儿中一个，但较轻情况，例如那些在儿童或成年期出现，可能更频繁发生。 FDA的药品评价和研究中心中药物评价III室副主任Amy G. Egan，M.D.，M.P.H.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。” Strensiq接受突破性治疗指定因为它是第一个和唯一的为围产期，婴儿和青少年发病HPP 的治疗。这个突破性治疗指定程序鼓励FDA与承办单位协同工作，通过提供及时建议和相互作用交流，帮助加快对严重或危及生命情况重要新药发展和审评。除了作为突破性治疗指定， FDA授予Strensiq孤儿药物指定因为它治疗一种疾病在美国影响少于200,000例患者。 孤儿药物指定提供财政鼓励，像临床试验税收抵免，用户费用减免，和上市专有权促进罕见疾病药物开发。Strensiq还被授予优先审评，它是授予在治疗一种严重情况显示在安全性或有效性显著改进的药物的申请。此外，Strensiq的制造商被授予一个罕见儿童疾病优先审评凭证 – 一个条款意向鼓励为罕见儿童疾病的预防和治疗新药和生物制品的发展。这个药物的发展还部分被FDA孤儿产品授权程序支持，它提供为罕见病或情况中使用产品的安全性和/或有效性临床研究。 Strensiq是通过每周3或6次注射给药。Strensiq通过替代酶(被称为组织非特异性碱性磷酸酶)负责在正常组织中必须矿物质的形成起作用，它曽显示改善患者结局。 在99例患者有围产期(在子宫内发生疾病和出生时明显)，婴儿- 或青少年-发病HPP，患者接受治疗直至6.5岁在四项前瞻性，开放研究期间确定Strensiq的安全性和疗效。研究结果显示有围产期-和婴儿发病HPP 患者用Strensiq治疗总生存和无需呼吸机生存(无呼吸机生存)有改进。在1岁时97%被治疗患者与之比较从研究组天然病史选择的对照患者为42%。相似地，在1岁时无呼吸机生存率对被治疗患者为85%，与之比较天然病史对照患者低于50%。 有青少年-发病HPP患者用Strensiq治疗与从天然病史数据库选择的对照患者比较显示生长和骨健康的改进。所有被治疗患者有低体重或短身高改进或维持正常身高和体重。与之比较，接近20%对照患者有随时间生长延迟，身高或体重从儿童他们年龄身高和体重远低于正常偏移。青少年-发病患者还显示骨矿物质话的改进，如基于x-线影像在一个标尺测定评价佝偻病的严重程度和其他HPP-相关各个异常。所有被治疗患者显示在x-线上实质上佝偻病愈合而有些天然病史对照患者显示佝偻病体征随时间增加。 用Strensiq治疗患者中最常见副作用包括注射部位反应，超敏性反应(例如呼吸困难，恶心，眩晕和发热)，脂肪代谢障碍(脂肪组织丧失导致在皮肤上的压痕或脂肪组织的增厚导致皮肤下有肿块) 在注射部位，和眼和肾异位钙化. Strensiq是总部在英国Cheshire的Alexion Pharmaceuticals公司制造。 http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm468836.htm New Drugs Online Report for asfotase alfa Information Generic Name: asfotase alfa   Trade Name: Strensiq  Synonym: ENB-0040  Entry Type: New molecular entity   Development and Regulatory status UK: Launched  EU: Launched  US: Approved (Licensed)  UK launch Plans: Available only to registered users Actual UK launch date: September 2015  Comments Oct 15: Alexion announces that the annual average price will be $285,000 in the US, well below the $400,000 predicted by market analysts [12]. 27/10/2015 11:09:36  Oct 15: FDA approves Strensiq (asfotase alfa) for Perinatal-, Infantile- and Juvenile-Onset Hypophosphatasia [11].  27/10/2015 08:42:38  Sep 15: Launched in UK [10]. 06/10/2015 11:22:08  Sep 15: Approved in EU [9]. 03/09/2015 12:36:48  Jun 15: EU positive opinion for long-term enzyme replacement therapy in patients with paediatric-onset hypophosphatasia to treat the bone manifestations of the disease [8]. 26/06/2015 12:29:57  Mar 15: Filed in the US for treatment of patients with infantile- and juvenile-onset hypophosphatasia [7]. 05/03/2015 15:20:46  Sep 14: Filed in the EU via the centralised procedure [6]. 19/09/2014 12:02:10  March 14: No further updates.  27/03/2014 14:00:51  Aug 13: Expected launch in the US late 2014 [4]. 28/08/2013 09:37:03  Granted orphan drug status in the EU in 2008 (EU/3/08/594) [3]. 29/05/2013 08:30:14  May 13: FDA has designated breakthrough therapy status for perinatal-, infantile- and juvenile-onset HPP. The drug already has orphan drug and fast track status in the US [1]. 28/05/2013 22:26:29  Trial or other data Sep 13: Results from an ongoing multinational PII study in 15 infants and young children (<5 years) with hypophosphatasia (HPP). The study met its primary endpoint: asfotase alfa led to significant improvement in skeletal mineralization as assessed radiographically after 24 weeks of treatment, with a mean (SD) increase in RGI-C score of 1.74 (1.107) and a median increase of 2.00 (p=0.001). This response was observed as early as 12 weeks and improvement continued at 48 weeks. 93% of patients survived the first 48 weeks of treatment with 80% having improved respiratory status or requiring no respiratory support at the final analysis. Asfotase alfa was well-tolerated with no deaths, serious AEs or discontinuations deemed treatment-related. The most common AEs were mild to moderate injection site reactions,(66.7% of patients). The trial is continuing to enrol patients [5]. 24/09/2013 09:23:38 NCT01176266 is an open-label, multicentre, multinational 2-year PII/III study of the safety, efficacy and pharmacokinetics of asfotase alfa in 30 infants and children ≤ 5 years of age with hypophosphatasia. Patients will receive a total of 6 mg/kg/week of asfotase alfa by SC injection, either as 1mg/kg 6 times per week or 2mg/kg 3 times per week. The primary outcomes are the effect of asfotase alfa on skeletal manifestations of HPP using a qualitative Radiographic Global Impression of Change (RGI-C) scale and tolerability. The study started Jul 10 and is due to complete Dec 14 [2]. 29/05/2013 08:26:36 Evidence Based Evaluations NICE scope  http://www.nice.org.uk/guidance/indevelopment/gid-hypophosphatasiaasfotasealfaid758/documents  EPAR  http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/003794/WC500194340.pdf  NHSC/NIHR  http://www.hsc.nihr.ac.uk/files/downloads/2230/2528.be317e 2b.Asfotasealfa_Nov13.pdf  References   Available only to registered users  Category BNF Category: Drugs used in metabolic disorders (09.08.01) Pharmacology: recombinant human tissue non-specific alkaline phosphatase - Fc - deca-aspartate fusion protein   Epidemiology: Hypophosphatasia (HPP) is rare inherited form of rickets and osteomalacia caused by inactivating mutations in the gene encoding the tissue-nonspecific isoenzyme of alkaline phosphatase (TNSALP). Disease severity is inversely related to the age at symptom presentation. Prevalence is about 1:100,000 [2].   Indication: Hypophosphatasia  Method(s) of Administration   Subcutaneous injection  Company Information Name: Alexion  US Name: Alexion  Further Information Anticipated commissioning route (England) -  High cost drug list? Yes In NICE timetable: Yes  When: Apr / 2016  Note: www.nice.org.uk/guidance/indevelopment?type=hst  Implications Available only to registered users