EU/3/04/194: Orphan designation for the treatment of lipoprotein-lipase deficiency

Triglycerides are one of the basic chemical 'building blocks' from which fats are formed. Lipoprotein lipase (LPL) is the key enzyme in the use and transformation of triglyceride-rich lipoproteins and protects the human body against the excessive rise of triglycerides after every meal. LPL is produced by skeletal muscle cells and excreted into the circulation where it awaits the triglycerides for breakdown.

LPL deficiency is an inherited condition that results in extremely high concentrations of circulating triglyceride-rich lipoproteins. LPL deficiency usually presents itself at infancy or childhood. It is chronically debilitating with typical complaints of severe abdominal pain, repetitive colicky pains, repeated episodes of pancreatitis (inflammation of the pancreas) and often 'failure to thrive'.

At the time of designation, lipoprotein lipase deficiency affected approximately 0.02 in 10,000 people in the European Union (EU). This was equivalent to a total of around 930 people*, and is below the ceiling for orphan designation, which is 5 people in 10,000. This is based on the information provided by the sponsor and the knowledge of the Committee for Orphan Medicinal Products (COMP).

*Disclaimer: For the purpose of the designation, the number of patients affected by the condition is estimated and assessed on the basis of data from the European Union (EU 25), Norway, Iceland and Liechtenstein. At the time of designation, this represented a population of 464,200,000 (Eurostat 2004).

At the time of submission of the application for orphan designation, no satisfactory method had been authorised in the European Union for treatment of the condition. Treatment of patients with LPL deficiency primarily involved restriction of dietary fat to less than 20% of total calories. The dietary regimen was difficult for patients to adhere to and there was, therefore, often recurrent pancreatitis in these patients.

Adeno-associated viral vector expressing LPL is a medicinal product that uses a virus to carry the gene necessary for the production of the enzyme LPL. A virus is a small organism capable of introducing genetic material in cells. The type of virus (adeno-associated virus) used in this medicinal product is modified so as not to cause any disease in humans.

The evaluation of the effects of adeno-associated viral vector expressing LPL in experimental models is on-going. At the time of submission of the application for orphan designation, no clinical trials in patients with LPL deficiency had been initiated.

Adeno-associated viral vector expressing LPL was not marketed anywhere worldwide for LPL deficiency or designated as orphan medicinal product elsewhere for this condition, at the time of submission.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 5 February 2004 recommending the granting of this designation.

Update: Glybera (alipogene tiparvovec) was authorised in the EU on 25 October 2012. Glybera is indicated for adult patients diagnosed with familial LPL deficiency and suffering from severe or multiple pancreatitis attacks despite dietary fat restrictions. The diagnosis of LPL deficiency has to be confirmed by genetic testing. The indication is restricted to patients with detectable levels of LPL protein.

More information on Glybera can be found in the European public assessment report (EPAR) on the Agency's website.

• the seriousness of the condition;
• the existence of alternative methods of diagnosis, prevention or treatment;
• either the rarity of the condition (affecting not more than 5 in 10,000 people in the EU) or insufficient returns on investment.

Designated orphan medicinal products are products that are still under investigation and are considered for orphan designation on the basis of potential activity. An orphan designation is not a marketing authorisation. As a consequence, demonstration of quality, safety and efficacy is necessary before a product can be granted a marketing authorisation.