最近，荷兰生物技术公司uniQure研发的Glybera(alipogene tiparvovec)成为了欧洲首个被推荐上市的基因治疗药物。Glybera为单次注射剂，适用于严格限制脂肪饮食却仍然发生严重或反复胰腺炎发作的脂蛋白脂酶缺乏症(LPLD)患者。
脂蛋白脂酶缺乏症是一种罕见的严重遗传性疾病，而且目前无法治疗。其发病率约为1~2例/百万人。该病是由LP基因突变引起的，后者会使LPL蛋白的活性严重下降或丧失。LPL蛋白是一种分解乳糜微粒的酶，如果乳糜微粒不被分解，就会在血液中积聚而堵塞小血管，从而可能导致复发性或严重急性胰腺炎。
目前，唯一对脂蛋白脂酶缺乏症患者有帮助的是采取严格限制脂肪饮食，使每日通过脂肪获得的热量不超过总热量的20％。但要坚持这样的饮食习惯并不容易，因此许多患者因危及生命的胰腺炎而住院。基因治疗通过以有活性的基因取代患者DNA中有缺陷的基因而发挥疗效。Glybera利用一种腺相关病毒将有活性的LPL基因插入肌细胞中，从而使这些细胞能产生正常数量的酶。
Glybera即将为欧洲治疗孤儿病的首个基因疗法。脂蛋白脂酶缺乏症患者不敢吃正常的食物以免引起急性胰腺炎和导致急诊入院。如今，这些患者第一次有了治疗方法，不仅能降低出现严重病情的风险，而且只需单次注射即可多年受益。基因治疗将赋予这些患者分解血液中脂肪的能力。

关于Glybera(alipogene tiparvovec)
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。

Glybera
Active Substance: alipogene tiparvovec
Common Name: alipogene tiparvovec
ATC Code: C10 AX10
Marketing Authorisation Holder: uniQure biopharma B.V. 
Active Substance: alipogene tiparvovec
Status: Authorised
Authorisation Date: 2012-10-25
Therapeutic Area: Hyperlipoproteinemia Type I
Pharmacotherapeutic Group: Lipid modifying agents
Therapeutic Indication
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

GLYBERA AMT-010(alipogene tiparvovec)
New Drugs Online Report for alipogene tiparvovec
Information
Generic Name: alipogene tiparvovec  
Trade Name: Glybera 
Synonym: AMT 011, adeno-associated viral vector expressing lipoprotein lipase 
Entry Type: New molecular entity  
Development and Regulatory status
UK: Approved (Licensed) 
EU: Approved (Licensed) 
US: Phase III Clinical Trials 
UK launch Plans: Available only to registered users
Actual UK launch date:  
Comments
Mar 15; In June 2014, the company reported that initial launches in the EU are planned in Germany, UK, Netherlands, Sweden and Austria. In August 2014, they decided to incorporate 6 year follow-up data from the AMT011-05 study, in pricing and reimbursement applications. Subsequently, launch in Europe is expected Q1 2015 [13]
11/03/2015 12:20:01 
March 14: In July 2013, uniQure and Chiesi Farmaceutici SpA entered into a commercialisation agreement, whereby Chiesi was granted exclusive rights to commercialise alipogene tiparvovec (Glybera®) in Europe. No further updates re: estimated launch. [12]
27/03/2014 11:12:38 
Nov 12: Approved in the EU. Glybera is the first gene therapy licensed for use in the Western World (China has already approved a gene therapy). Launch is planned for 2013 & UniQure plans to file licence applications in the US & Canada [11].
02/11/2012 16:49:40 
Jul 12: CHMP has issued a positive opinion recommending marketing authorization as a treatment for lipoprotein lipase deficiency (LPLD) under exceptional circumstances. As part of the approval, treatment will be offered through dedicated centres with expertise in treating LPLD. uniQure has also committed to building a patient registry. The Company is now preparing to file in the US [10].
24/07/2012 09:06:40 
Apr 12: CHMP decision not to recommend approval maintained [9].
23/04/2012 10:31:49 
Jan 12: EU Standing Committee of the European Parliament discussed the implementation decision not to grant marketing authorisation for alipogene tiparvovec as recommended by the CHMP. No clear position in favour or against granting a marketing authorisation was reached. The Standing Committee considered it necessary to request additional information to the CHMP. A formal vote by the Standing Committee will be made on review of the additional information. It is currently unclear when a final decision will be reached. [7] 
30/01/2012 16:53:16 
Oct 11: CHMP has re-examined the initial opinion, and maintained its recommendation that Glybera should not be granted a marketing authorisation [6]. 
24/10/2011 16:28:47 
June 11: Amsterdam Molecular Therapeutics (AMT) has announced it filed a request for re-examination of the MAA with the EMA for Glybera. The Company expects that the re-examination of the dossier will be completed by the end of 2011. [5]
11/07/2011 08:25:06 
June 11: The CHMP concluded that the three studies in 27 pts presented in support of the MAA had not shown a consistent long-lasting benefit of aliopogene, there was insufficient evidence of a clinically relevant persistent lowering of blood fats or reduction in rate of pancreatitis & too little long-term data available. In view of the uncertainty over alipogene´s benefits & insufficient evidence of safety, the CHMP concluded that the benefits of alipogene had not been shown to outweigh its risks [4]. 
24/06/2011 17:02:46 
Jun 11: EU negative opinion for alipogene tiparvovec to treat adults with lipoprotein lipase deficiency having hyperchylomicronaemia or history of acute pancreatitis [4].
24/06/2011 14:17:29 
Orphan drug status in EU. Around 1000 people in EU affected [3].
02/06/2011 11:45:49 
Aug 10: The EMA requested further data, but not an additional clinical trial, in May 10. The company intend to respond by the end of 2010 and anticipate approval in mid-2011 [2].
01/09/2010 08:47:42 
Jan 10: Filed in EU for lipoprotein lipase deficient patients [1].
13/01/2010 18:53:28 
Trial or other data
Mar 12: Results of an open label clinical trial (CT-AMT-011-02) announced: 5 LPLD pts were administered alipogene tiparvovec (1012 genome copies/kg). The triglyceride (TG) content of the chylomicron fraction and the chylomicron-triglyceride (TG)/total plasma TG ratio were reduced throughout the postprandial period. The postprandial peak chylomicron level and chylomicron AUC were greatly reduced (by 79% and 93%, 6- and 24 hours after the test meal, respectively). There were no significant changes in plasma fatty acid and glycerol appearance rates. Plasma glucose, insulin and C-peptide also did not change [8].
29/03/2012 11:41:38
Company has conducted two clinical studies for lipoprotein lipase deficiency (LPLD) in Europe and Canada and long term follow-up from these is ongoing, as is a further study in Canada. In these three studies Glybera has been associated with a decrease in the incidence of pancreatitis, the most debilitating complication of LPLD [1].
13/01/2010 18:55:16
Evidence Based Evaluations
EPAR  http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/002145/WC500135476.pdf 
NHSC  http://www.haps.bham.ac.uk/publichealth/horizon/outputs/documents/2009/jan-apr/AMT-011.pdf 
References  
Available only to registered users
 Category
BNF Category: Metabolic disorders (09.08)
Pharmacology: Gene transference, Lipoprotein lipase stimulants  
Epidemiology: Debilitating and potentially lethal orphan disease caused by mutations in the LPL gene [1]. Around 1 in 1,000,000 people are affected; equates to 52 people in England and Wales (NHSC)  
Indication: Hyperlipoproteinaemia 
Additional Details: Lipoprotein lipase deficiency 
Method(s) of Administration  
Intramuscular 
Company Information
Name: Chiesi 
US Name: Amsterdam Molecular Therapeutics 
Further Information
Anticipated commissioning route (England) NHSE 
High cost drug list? Yes
Tariff Not routinely commissioned by NHSE - IFR approval [14]
Implications Available only to registered users