02 November 2012

AMSTERDAM UNIQURE BV.: GLYBERA for Lipoprotein Lipase Deficiency


Glybera® (alipogene tiparvovec) overview
Glybera has been developed for the treatment of lipoprotein lipase deficiency (LPLD), a very rare inherited condition that is associated with increased levels of chylomicrons, particles carrying certain fat in the blood. LPLD is caused by errors in the gene that codes for a protein called lipoprotein lipase (LPL). The LPL protein has an important role in dealing with the fats from the food that we eat. When the LPL protein does not work properly, or there is not enough of it, fat levels in the blood increase dramatically.
Glybera introduces a normal, healthy LPL gene into the body so that it can make functional LPL protein. The LPL gene is packaged in a delivery vector derived from adeno-associated virus (AAV), serotype 1, which has a natural propensity towards muscle cells. As muscle cells are normally the most important tissue contributing to healthy LPL protein production, this particular AAV is very suitable for correction of LPLD. Glybera is administered via a one-time series of small intramuscular injections in the legs.

Glybera Clinical Data
Glybera® has been tested in three interventional clinical studies conducted in the NETHERLANDS and  CANADA, in which a total of 27 LPLD patients were administered the therapy. In one of the studies postprandial chylomicron metabolism was studied. In addition, a case note review study of historical data on hospital presentations due to abdominal pain from 17 patients already treated with Glybera and 5 untreated LPLD patients has been concluded.

In all studies the therapy proved to be well tolerated and no material safety concerns were observed. Data from the clinical trials indicates that fat concentrations in blood were reduced after therapy in nearly all patients between 3 and 12 weeks after injection of Glybera. A single dose administration of Glybera resulted in a long-term presence and biological activity of the protein in the injected muscle. Importantly, a single administration of Glybera resulted in long-term, clinically important reduction in the occurrence of acute pancreatitis episodes – which represent the most debilitating complication of LPLD. The case note review study showed a significant reduction in the frequency of hospital presentations for pancreatitis and severe abdominal pain related to the pancreas. Chylomicron metabolism, poor prior to Glybera administration, proved to be much improved at 14 and 52 weeks after one-time Glybera administration, indicating sustained LPL activity in the blood, which could be taken as a marker of efficacy.

Glybera Regulatory Status EU
On 20 July 2012 the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) issued a positive opinion that recommends marketing authorization of Glybera® (alipogene tiparvovec) as a treatment for lipoprotein lipase deficiency (LPLD) under exceptional circumstances.
The Company is expecting a final approval from the European Commission within three months after the CHMP decision.

After the positive recommendation, Glybera is poised to become the first in a class of gene therapy products approved in Europe to treat orphan diseases, rare conditions with a very high unmet medical need. Marketing authorization covers all 27 European Union member states.

As part of the approval, treatment with Glybera will be offered through dedicated centers of excellence with expertise in treating LPLD and by specially trained doctors to ensure ongoing safety of this novel treatment paradigm. The Company is now preparing to apply for regulatory approval in the US, Canada, and other markets.

COST: approx.$1.600.000 per patient.