部份中文Glybera处方资料（仅供参考） 商品名称：Glybera 通用名称：alipogene tiparvovec 成    分：alipogene tiparvovec 批准日期：25/10/2012 上市许可：uniqure生物制药B.V. 药物治疗组：血脂调节剂 治疗领域：高脂蛋白血症I型 适应症 Glybera是indicato诊断为家族性脂蛋白脂酶缺乏症（LPLD）和尽管饮食中脂肪的限制严重或多重胰腺炎发作的痛苦成年患者。LPLD的诊断必须通过基因检测来确认。该指示被限制为患者LPL蛋白的可检测水平。研究人员发现，缺乏脂蛋白脂酶的患者使用一次Glybera之后，就可以显著减少急性胰腺炎发病率 治疗原理 Glybera利用一种腺联病毒(AAV)将一个功能性的LPL基因拷贝传递给骨骼肌。北卡罗来纳大学教堂山分校基因治疗中心主任Jude Salmuski 曾在上世纪80年代初创先利用AAV作为基因治疗载体。Salmuski表示，AAV有几个特性，使得它成为一种有吸引力的基因治疗载体。AAV DNA很少整合到宿主基因组中，减少了基因整合的促癌性突变风险。相反的是，AAV可以潜藏，作为染色体外DNA片段继续存在。此外，由于AAV对人类是不致病的。 为了利用这种AAV载体，Glybera的开发这着移除了病毒基因，用治疗DNA替换了96%的AAV基因组。这一治疗DNA由LPL基因和来自其他病毒的启动子和调控元件组成。他们还添加了将载体引导至骨骼肌的蛋白质 疗效 在两项II/III期临床试验中，LPLD患者的大腿肌肉接受了一系列的注射，随后数周给予免疫抑制药物减弱对病毒衣壳的免疫反应——Gelsinger的最终死亡原因。在注射12周后，治疗成功地降低了血液中甘油三酯水平，在之后长达2年的时间大大减低了胰腺炎发病率。谢布鲁克大学大学内分泌科医生André Carpentier说患者甚至可以放松饮食限制，也帮助提高了生活质量。更为重要的是，迄今只报道了一次值得关注的副作用——引起了发烧，但在12个小时内便会消除。 Glybera® (alipogene tiparvovec) Glybera® (alipogene tiparvovec), the first gene therapy approved in the Western world, is used to treat lipoprotein lipase deficiency (LPLD or familial hyperchylomicronemia), a very rare inherited condition that is associated with increased levels of fat in the blood. Without lipoprotein lipase (LPL), these patients have significantly increased levels of chylomicrons that carry fat throughout the body. Accumulation of these chylomicrons in the pancreas can lead the the often painful and potentially fatal condition pancreatitis. Gene therapy using an AAV vector. A new gene is inserted into a cell using the AAV protein shell. The new gene often integrates in a precise location and then makes functional protein to treat a disease. uniQure announced today it has received approval from the European Commission for the gene therapy Glybera® (alipogene tiparvovec), a treatment for patients with lipoprotein lipase deficiency (LPLD, also called familial hyperchylomicronemia) suffering from recurring acute pancreatitis. Patients with LPLD, a very rare, inherited disease, are unable to metabolize the fat particles carried in their blood, which leads to inflammation of the pancreas (pancreatitis), an extremely serious, painful, and potentially lethal condition. The approval makes Glybera the first gene therapy approved by regulatory authorities in the Western world. "Glybera's approval means LPLD patients, for the first time, have a medical treatment option for a very complex and severe disease," said Professor John Kastelein of the Department of Vascular Medicine at the Academic Medical Center of the University of Amsterdam, the Netherlands. "LPLD leads to acute and recurrent pancreatitis attacks, and in many patients causes early onset diabetes and cardiovascular complications. This therapy will have a dramatic impact on the lives of these patients. Currently their only recourse is to severely restrict the amount of fat they consume. By helping to normalize the metabolism of fat, Glybera prevents inflammation of the pancreas thereby averting the associated pain and suffering and, if administered early enough, the associated co-morbidities." As part of the approval, patients will receive treatment with Glybera through dedicated centers of excellence and by specially trained doctors. uniQure will also build a patient registry to further improve the understanding of this devastating, under-researched disease and the effects of Glybera treatment. Marketing Authorisation covers all 27 European Union member states. uniQure is preparing to apply for regulatory approval in the US, Canada, and other markets. About Glybera® uniQure has developed Glybera as a therapy for patients with the genetic disorder lipoprotein lipase deficiency, an orphan disease for which no treatment existed. The disease is caused by mutations in the LPL gene, resulting in highly decreased or absent activity of LPL enzyme in patients. This enzyme is needed in order to break down large fat-carrying particles that circulate in the blood after each meal. When such particles, called chylomicrons, accumulate in the blood, they may obstruct small blood vessels. Excess chylomicrons result in recurrent and severe acute inflammation of the pancreas, called pancreatitis, the most debilitating complication of LPLD. Glybera has orphan drug designation in the EU and US. LPL Deficiency affects 1-2 persons per million. Glybera has been tested in three interventional clinical studies conducted in the Netherlands and in Canada, in which a total of 27 LPLD patients participated. In all three clinical trials, Glybera was well tolerated, with no relevant safety issues observed. Data from these clinical trials indicate that a single dose administration of Glybera resulted in a long-term biological activity of the LPL protein. Lipoprotein lipase is a key 'first step' enzyme in the metabolism of lipoproteins following fat intake with diet. In clinical studies a transient reduction in triglycerides for up to 12 weeks in individual patients could be observed. Furthermore, Glybera allows expression of the LPL protein in injected muscle which is reflected by the improvement of postprandial chylomicron (CM) metabolism observed in a small subset of patients. Glybera (alipogene tiparvovec) contains the human lipoprotein lipase (LPL) gene variant LPL S447X in a vector. The vector comprises a protein shell derived from adeno-associated virus serotype 1 (AAV1), the promoter, a posttranscriptional regulatory element and AAV2 derived inverted terminal repeats. Glybera is indicated for adult patients diagnosed with familial lipoprotein lipase deficiency (LPLD) and suffering from severe or multiple pancreatitis attacks despite dietary fat restrictions. The diagnosis of LPLD has to be confirmed by genetic testing. The indication is restricted to patients with detectable levels of LPL protein. The most commonly reported adverse reaction is pain in extremity occurring in approximately one third of patients.  Given the small patient population and size of the cohorts, observed adverse reactions do not provide a complete perspective on the nature and frequency of these events.    Glybera(alipogene tiparvovec)成为欧洲首个基因治疗药物 2014年3月17日,荷兰小型生物技术公司uniQure 3月17日公布了对已接受Glybera治疗的脂蛋白脂肪酶缺乏症（LPLD）患者回顾性收集资料的初步分析数据。该项分析涵括了13例患者治疗后长达6年的随访数据，这些患者均满足Glybera在欧盟的标签适应症要求。 Glybera是一种基因疗法，于2012年10月获欧盟批准，用于治疗一种极其罕见的遗传性、代谢性疾病——脂蛋白脂肪酶缺乏症（LPLD）。 一个由独立专家组成的外部仲裁委员会对每例患者的档案进行了审查。该项分析，将患者接受Glybera治疗前6年和治疗后6年的时间段进行了对比，以评估既往有严重或反复胰腺炎病史的每例LPLD患者，分别在这2个时间段里遭受胰腺炎发作的次数和严重程度。审查结果表明，Glybera在新胰腺炎事件风险（包括重症胰腺炎事件的发生）方面提供了长期有益影响。这些结果与Glybera治疗后长达3年的复查结果所表现出的积极趋势相符。 LPLD是一种罕见病，发病率不超过百万分之一或二。LPLD患者无法处理血液中的脂肪颗粒，具有急性及潜在致命性胰腺炎症风险。在临床试验中，LPLD患者接受一次Glybera治疗后，就可以显著降低急性胰腺炎发病率。 关于Glybera： Glybera是一种基因疗法，利用一种腺相关病毒（AAV）将一个功能性LPL基因拷贝传递给骨骼肌，该药用于治疗一种极其罕见的遗传性、代谢性疾病——脂蛋白脂肪酶缺乏症（LPLD）。 Glybera于2012年10月获欧盟批准，是欧洲获批的首个基因治疗药物，是基因治疗领域的重大推动力，同时标志着基因治疗的一个里程碑。相对于传统的蛋白替代策略，基因疗法能够提供更高的利益，因为基因治疗恢复了自然的身体机能，而不仅仅是短期修复。