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.]]
(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
. European Agency Backs Approval of a Gene Therapy
July 20, 2012 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.Gallagher, James. (2012-11-02) BBC News – Gene therapy: Glybera approved by European Commission
. Bbc.co.uk. Retrieved on 2012-12-15.
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.
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 compared to retrovirus
es, 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
. 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 and as of 2015 a total of 27 individuals had been involved in Phase III testing.
It was approved in Europe in 2012.
Alipogene tiparvovec was expected to cost around $1.6 million per treatment in 2012, revised to $1 million in 2015, making it the most expensive medicine in the world at the time. Gene therapy approved in Europe for first time
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.
As of 2016, only one person had been treated with the drug.
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.