Alipogene tiparvovec

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Alipogene tiparvovec
Clinical data
Trade names Glybera
AHFS/ UK Drug Information
Routes of
Intramuscular injection
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
CAS Number
  • none
Gene therapy using an AAV vector. A new gene is inserted into a cell using the AAV protein shell. Once inside the nucleus, the new gene makes functional protein to treat a disease.

Alipogene tiparvovec (marketed under the trade name Glybera) is a gene therapy treatment, developed and marketed by uniQure N.V., that compensates for lipoprotein lipase deficiency (LPLD), a rare inherited disorder which can cause severe pancreatitis.[1] In July 2012, the European Medicines Agency recommended it for approval, the first recommendation for a gene therapy treatment in either Europe or the United States. The recommendation was endorsed by the European Commission in November 2012.[2][3]


The adeno-associated virus serotype 1 (AAV1) viral vector delivers an intact copy of the human lipoprotein lipase (LPL) gene to muscle cells. The LPL gene is not inserted into the cell's chromosomes but remains as free floating DNA in the nucleus. The injection is followed by immunosuppressive therapy to prevent immune reactions to the virus.[4]

Data from the clinical trials indicates that fat concentrations in blood were reduced between 3 and 12 weeks after injection, in nearly all patients. The advantages of AAV include apparent lack of pathogenicity, delivery to non-dividing cells, and much smaller risk of insertion[5] compared to retroviruses, which show random insertion with accompanying risk of cancer. AAV also presents very low immunogenicity, mainly restricted to generating neutralizing antibodies, and little well defined cytotoxic response.[6][7][8] The cloning capacity of the vector is limited to replacement of the virus's 4.8 kilobase genome.


LPLD is a rare condition (prevalence worldwide 1–2 per million) and as such its clinical testing has involved unusually small cohort sizes. The first main trial (CT-AMT-011-01) involved just 14 subjects[9] and as of 2015 a total of 27 individuals had been involved in Phase III testing.[10]

It was approved in Europe in 2012.[11]

Alipogene tiparvovec was expected to cost around $1.6 million per treatment in 2012,[12] revised to $1 million in 2015,[13] making it the most expensive medicine in the world at the time.[14]

In 2015 UniQure dropped its plan to approval in the US and exclusively licensed rights to sell the drug in Europe to Chiesi Farmaceutici S.p.A..[11]

As of 2016, only one person had been treated with the drug.[11]

In April 2017, uniQure announced that it will not pursue the renewal of the marketing authorization in Europe when it was scheduled to expire the coming October, due to lack of demand.[15]

See also[edit]


  1. ^ European Agency Backs Approval of a Gene Therapy July 20, 2012
  2. ^ Gallagher, James. (2012-11-02) BBC News – Gene therapy: Glybera approved by European Commission. Retrieved on 2012-12-15.
  3. ^ Richards, Sabrina. "Gene Therapy Arrives in Europe". The Scientist. Retrieved 16 November 2012. 
  4. ^ "Gene Therapy Arrives in Europe". TheScientist. November 6, 2012. 
  5. ^ Valdmanis PN, Lisowski L, Kay MA (November 2012). "rAAV-mediated tumorigenesis: still unresolved after an AAV assault.". Molecular Therapy. 20 (11): 2014–17. PMC 3498811Freely accessible. PMID 23131853. doi:10.1038/mt.2012.220. 
  6. ^ Chirmule N, Propert K, Magosin S, Qian Y, Qian R, Wilson J (September 1999). "Immune responses to adenovirus and adeno-associated virus in humans". Gene Therapy. 6 (9): 1574–83. PMID 10490767. doi:10.1038/ 
  7. ^ Hernandez YJ, Wang J, Kearns WG, Loiler S, Poirier A, Flotte TR (1 October 1999). "Latent Adeno-Associated Virus Infection Elicits Humoral but Not Cell-Mediated Immune Responses in a Nonhuman Primate Model". Journal of Virology. 73 (10): 8549–58. PMC 112875Freely accessible. PMID 10482608. 
  8. ^ Ponnazhagan S, Mukherjee P, Yoder MC, et al. (April 1997). "Adeno-associated virus 2-mediated gene transfer in vivo: organ-tropism and expression of transduced sequences in mice". Gene. 190 (1): 203–10. PMID 9185868. doi:10.1016/S0378-1119(96)00576-8. 
  9. ^ Stroes, E. S.; Nierman, M. C.; Meulenberg, J. J.; Franssen, R.; Twisk, J.; Henny, C. P.; Maas, M. M.; Zwinderman, A. H.; Ross, C.; Aronica, E.; High, K. A.; Levi, M. M.; Hayden, M. R.; Kastelein, J. J.; Kuivenhoven, J. A. (2008). "Intramuscular Administration of AAV1-Lipoprotein LipaseS447X Lowers Triglycerides in Lipoprotein Lipase-Deficient Patients". Arteriosclerosis, Thrombosis, and Vascular Biology. 28 (12): 2303–2304. ISSN 1079-5642. doi:10.1161/ATVBAHA.108.175620. 
  10. ^ Scott, Lesley J. (2015). "Alipogene Tiparvovec: A Review of Its Use in Adults with Familial Lipoprotein Lipase Deficiency". Drugs. 75 (2): 175–182. ISSN 0012-6667. doi:10.1007/s40265-014-0339-9. 
  11. ^ a b c Regalado, Antonio (May 4, 2016). "The World’s Most Expensive Medicine Is a Bust". MIT Technology Review. 
  12. ^ Jeanne Whalen (November 2, 2012). "Gene-Therapy Approval Marks Major Milestone". Wall Street Journal. 
  13. ^ Chris Morrison (March 3, 2015). "$1-million price tag set for Glybera gene therapy". TradeSecrets. 
  14. ^ Gene therapy approved in Europe for first time
  15. ^ Sagonowsky, Eric (April 20, 2017). "With its launch fizzling out, UniQure gives up on $1M+ gene therapy Glybera". FiercePharma.