英文药名：STRENSIQ Subcutaneous Injection（Asfotase Alfa(Genetical Recombination)）

中文药名：重组融合糖蛋白注射液

日文药名：ストレンジック皮下注

生产厂家：Alexion制药公司
治疗类别名称
低磷酸酯酶治疗药物
欧文商標名
STRENSIQ Subcutaneous Injection
一般名
アスホターゼ　アルファ（遺伝子組換え）
一般名
（欧名） Asfotase Alfa(Genetical Recombination)
本質
Asuhotaze alpha是重组融合糖蛋白，人组织的非特异性碱性磷酸酶的1-485个催化结构域，488-714个对应于人IgG1的Fc结构域，10个天冬酰胺在C末端的酸残基为界。 Asuhotaze阿尔法从中国仓鼠卵巢细胞产生。 Asuhotaze字母组成的糖蛋白亚基2的726个氨基酸残基组成（分子量约18万）
药效药理
作用机序
低磷酸酯酶是由基因的突变在组织非特异性碱性磷酸酶（TNSALP）遗传性疾病。通过TNSALP活性降低，在体内基质如无机焦磷酸（PPI）和吡哆醛-5'-磷酸（PLP）被累积，并显示出骨矿化疾病，症状如呼吸衰竭和癫痫发作。这种药物是一种糖蛋白通过添加Fc区和十天冬氨酸肽的人免疫球蛋白（Ig）G1至人类TNSALP的催化区。这种药物主要是分解的PPi抑制骨矿化骨组织中，通过产生的无机磷（Pi），以生成与钙羟基磷灰石，促进骨矿化。
药理作用
预防性给药
是一种低磷酸酶症模型动物Akp2-/-小鼠中，当预防性给药至15天出生后从出生Asuhotazeα（基因重组）的时间时，观察到的改进的骨矿化异常和生长的。此外，当它是从出生预防性施用直至分娩后43-52天，观察到的存活改善。
治疗性给药
Akp2-/-小鼠，当他们的Asuhotaze15天α（重组）出生直到43天，骨矿化异常，改善的生长和存活，观察后治疗给药。
审批条件
在制定药品风险管理计划，正确实施的。
临床试验的情况下在国内已经非常有限，上市后，通过在复试期间实施的所有管理的情况下使用效果调查，并了解这种药物的使用患者的背景资料的安全性和有效性的数据是初采集，采取必要的措施，正确使用这种药物。
适应证和用途
用于治疗低磷酸酯酶
剂量和给药方法
每周一次1mg的/kg至6次，或一次为2mg/每周公斤予三次皮下施用。另外；根据患者的病情，体重损失为适当。
包装规格
皮下注射：12毫克/0.3毫升*1瓶
皮下注射：18毫克/0.45毫升*1瓶
皮下注射：28毫克/0.7毫升*1瓶
皮下注射：40毫克/1毫升*1瓶
皮下注射：80毫克/0.8毫升*1瓶

生产厂家：Alexion制药日本公司
注：以上部份中文资料仅供参考，使用以原处方为准：http://www.kegg.jp/medicus-bin/japic_med?japic_code=00065743
Strensiq(asfotase alfa) Receives Marketing Approval in Japan for Treatment of Patients with Hypophosphatasia (HPP)
–First Approved Treatment for Japanese Patients Suffering from HPP, a Life-New Drug Application (NDA) for the useThreatening Ultra-Rare Metabolic Disorder–
Strensiq(asfotase alfa) as a treatment for patients in Japan with hypophosphatasia (HPP), a life-threatening, ultra-rare metabolic disorder. Strensiq, a bone-targeted enzyme replacement therapy, is the first therapy approved in Japan for the treatment of patients with HPP.
“The rapid approval of the Strensiq NDA in Japan underscores the devastating nature of HPP and the life-transforming impact that Strensiq can provide to Japanese patients living with HPP,” said David Hallal, Chief Executive Officer of Alexion. “We are delighted that this regulatory approval in Japan marks the first treatment option for patients with HPP, and we look forward to urgently working with the healthcare authorities to make Strensiq available to Japanese patients who can benefit from this therapy. I would also like to thank the investigators, patients, and their families in Japan who participated in the clinical trial that led to this approval.”
HPP is a genetic, progressive, ultra-rare metabolic disease in which patients experience devastating effects on multiple systems of the body, leading to debilitating or life-threatening complications. It is characterized by defective bone mineralization that can lead to deformity of bones and other skeletal abnormalities, as well as systemic complications such as profound muscle weakness, seizures, pain, and respiratory failure leading to premature death in infants.1-5 As reflected in the prescribing information in Japan, infants with HPP treated with Strensiq had 84% overall survival, as estimated by Kaplan-Meier analysis, at 168 weeks.
“Hypophosphatasia is an ultra-rare disease with diverse clinical symptoms that may be difficult to diagnose. It can be a lethal disease in Japanese newborns and infants which has led to significant challenges since there have been no approved treatment options,” said Professor Ozono, Department of Pediatrics Osaka University. “I am greatly delighted that the first treatment has been approved for HPP. The patients and physicians in Japan who participated in the Strensiq clinical trials have played a critical role in generating valuable data and we appreciate their contributions in enabling the approval of Strensiq. I look forward to using Strensiq in clinical practice and continuing to advance the understanding of HPP diagnosis and treatment.”
“Today’s approval marks a major turning point for patients and their families in Japan who have waited a long time for a treatment for hypophosphatasia,” said Mr. Hara, Director of HypoPhosPhatasia Support Association of Japan. “The approval of Strensiq offers great hope to patients who previously suffered in the absence of an effective therapy, as well as to the healthcare professionals and families who care for and support them.”
Alexion has submitted a Biologics License Application for Strensiq with the U.S. Food and Drug Administration, which was accepted for priority review, and received a positive CHMP opinion recommending marketing authorization for Strensiq for patients with pediatric-onset HPP in Europe. Regulatory decisions in the U.S. and Europe are expected in the second half of 2015.
Clinical Data
The approval of Strensiq in Japan was based on clinical data from three pivotal prospective studies and their extensions, a retrospective natural history study in infants, and one investigator-sponsored study in Japan. The pivotal studies comprised 71 patients, including five Japanese patients, with infantile and juvenile-onset HPP (ages 1 day to 65 years). Study results showed that patients with infantile-onset HPP (ages ≤5 years at enrollment) treated with Strensiq demonstrated rapid and sustained improvements in bone mineralization, as measured by the Radiographic Global Impression of Change (RGI-C) scale, which evaluates the severity of rickets based on X-ray images. In addition, infants with HPP treated with Strensiq had 84% overall survival, as estimated by Kaplan-Meier analysis, at 168 weeks. Patients with juvenile-onset HPP treated with Strensiq demonstrated superior improvements in bone health compared to a control group of HPP patients selected from a natural history database, as well as improvements in ambulation, physical function and growth.
The most frequently reported adverse events observed with Strensiq treatment in clinical studies were injection site reactions and injection-associated reactions. Most of these adverse events were mild to moderate in severity. Serious injection-associated reactions were reported in two patients, with neither patient discontinuing Strensiq treatment: one patient with infantile-onset HPP reported fever and chills, and one patient with juvenile-onset HPP reported numbness of lips, leg pain, chills, and headache.
About Hypophosphatasia (HPP)
HPP is a genetic, chronic and progressive ultra-rare metabolic disease characterized by defective bone mineralization that can lead to destruction and deformity of bones, profound muscle weakness, seizures, respiratory failure and premature death.1-5
HPP is caused by mutations in the gene encoding an enzyme known as tissue non-specific alkaline phosphatase (TNSALP).1,2 The genetic deficiency in HPP can affect people of all ages.1 HPP is classified by the age of the patient at the onset of symptoms of the disease, with infantile- and juvenile-onset HPP defined as manifestation of the first symptom prior to 18 years of age.
HPP can have devastating consequences for patients at any stage of life.1 In a natural history study, infants who had their first symptom of HPP within the first 6 months of life had high mortality, with an overall mortality rate of 73% at 5 years.6 In these patients, mortality is primarily due to respiratory failure.1,5,7 In patients surviving to adolescence and adulthood, long-term clinical sequelae include recurrent and non-healing fractures, profound muscle weakness, debilitating pain and the requirement for ambulatory assistive devices such as wheelchairs, wheeled walkers and canes.1,4
About Strensiq(asfotase alfa)
Strensiq? (asfotase alfa) is a first-in-class bone-targeted enzyme replacement therapy designed to address the underlying cause of HPP—deficient alkaline phosphatase (ALP). By replacing deficient ALP, treatment with Strensiq aims to improve the elevated enzyme substrate levels and improve the body's ability to mineralize bone, thereby preventing serious skeletal and systemic patient morbidity and premature death.
Strensiq has been granted orphan drug designation by the U.S. Food and Drug Administration (FDA), the European Medicines Agency (EMA), and the Japanese Ministry of Health, Labour and Welfare (MHLW). Alexion has submitted a Biologics License Application for Strensiq with the U.S. Food and Drug Administration, which was accepted for priority review, and a Marketing Authorization Application for Strensiq in Europe is under review.
Strensiq-首个低磷酸酯酶症（HPP）治疗药物
Strensiq由Alexion公司自主研发，获欧盟批准作为一种长期的骨靶向酶替代疗法，用于超罕见的小儿发病低磷酸酯酶症（HPP）患者的治疗。
在欧盟，Strensiq是获批治疗HPP的首个药物。低磷酸酯酶症（HPP）是一种极为罕见的，渐进式的遗传性代谢紊乱疾病，患者机体多系统受损，导致身体虚弱甚至威胁其生命。低磷酸酯酶症（HPP）可使患者骨矿物质化，导致骨畸形及其他骨骼异常性疾病，还可导致多系统并发症，例如严重的肌无力、抽搐、疼痛和可导致婴儿夭折的呼吸困难。