alipogene tiparvovec (Glybera®)
Reference No. 645 Publication date: 18/03/2013
Appraisal information
alipogene tiparvovec (Glybera®) 3 × 10¹² genome copies/ml solution for injection
Company:  UniQure Biopharma BV 
BNF category: Nutrition and blood
 NMG meeting date: Not scheduled 
 AWMSG meeting date: Not scheduled 
Submission Type:  Nonsubmission 
Status:  Not endorsed 
 Advice No:  Not available 
 Ministerial ratification:  18/03/2013 
AWMSG advice
In the absence of a submission from the holder of the marketing authorisation, alipogene tiparvovec (Glybera®) cannot be endorsed for use within NHS Wales for the treatment of adult patients diagnosed with familial lipoprotein lipase deficiency and suffering from severe or multiple pancreatitis attacks despite dietary fat restrictions.


Glybera – The Most Expensive Drug in the world & First Approved Gene Therapy in the West
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.
2, 2012 – 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.
“The final approval of Glybera from the EC marks a major step forward in making gene therapies available not only for LPLD but also for a large number of rare diseases with a very high unmet medical need,” says Jörn Aldag, CEO of uniQure.  “The EC’s approval is an important validation of our innovative product platform and offers strong support for our other advanced development programs, which focus on acute intermittent porphyria, Sanfilippo B, hemophilia B and Parkinson’s disease.”
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. For further information on LPLD visit www.lpldeficiency.com.
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 LPLS447X 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。