EU/3/10/827: Orphan designation for the treatment of lysosomal acid lipase deficiency

Lysosomal acid lipase deficiency is an inherited disease caused by the lack of one of the enzymes needed to break down fats within cells. In the absence of this enzyme, called lysosomal acid lipase, fats accumulate in the body's cells and tissues, causing symptoms such as growth failure, enlarged liver, diarrhoea and malabsorption (when nutrients from food are not easily absorbed during digestion).

Lysosomal acid lipase deficiency is a severe and life-threatening disease which, in its most severe form, is usually fatal in the first year of life.

At the time of designation, lysosomal acid lipase deficiency affected less than 0.2 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 10,000 people*, and is below the threshold 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 27), Norway, Iceland and Liechtenstein. At the time of designation, this represented a population of 506,300,000 (Eurostat 2010).

At the time of designation, no satisfactory methods were authorised in the EU for the treatment of lysosomal acid lipase deficiency. Patients were advised to follow a diet low in fats. In some cases, haematopoietic (blood) stem cell transplantation had been used, but with modest results. This is a complex procedure where the patient receives stem cells from a matched donor to help restore the bone marrow.

Recombinant human lysosomal acid lipase is an 'enzyme replacement therapy' that is expected to work by replacing the missing enzyme in lysosomal acid lipase deficiency, helping to break down fats and stopping them building up in the body's cells.

Recombinant human lysosomal acid lipase is produced by a method known as 'recombinant DNA technology': it is extracted from the eggs of hens that have been given genes that make them able to produce an exact copy of the human enzyme in their eggs.

The effects of recombinant human lysosomal acid lipase have been evaluated in experimental models.

At the time of submission of the application for orphan designation, no clinical trials with the medicine in patients with lysosomal acid lipase deficiency had been started.

At the time of submission, recombinant human lysosomal acid lipase was not authorised anywhere in the EU for the treatment of lysosomal acid lipase deficiency. Orphan designation of the medicine had been granted in the United States of America for this condition.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 7 October 2010 recommending the granting of this designation.

• 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.