EU/3/07/446: Orphan designation for the treatment of metachromatic leukodystrophy

Metachromatic leukodystrophy is a chronic hereditary disease. It is caused by the lack of an enzyme (a protein that speeds up the conversion of certain substances into other substances) called arylsulfatase A. This causes a toxic accumulation of lipid compounds called sulfatides, particularly in the cells of the nervous system. The nervous system is progressively damaged resulting in symptoms such as walking difficulties, mental deterioration and other symptoms related to the impairment of the nervous system in the affected patients. The disease is chronically debilitating and life-threatening.

At the time of designation, metachromatic leukodystrophy affected less than 0.5 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 25,000 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 500,300,000 (Eurostat 2007).

No satisfactory methods exist that were authorised for the treatment of metachromatic leukodystrophy at the time of application. Only temporary symptomatic treatments were available. In a minority of cases, haematopoetic stem cell transplantation (bone marrow transplantation) has been used as treatment.

The treatment with autologous CD34+ cells transfected with lentiviral vector containing the human arylsulfatase A cDNA includes taking cells called CD34+ cells from the blood of the affected patient and introducing the gene for the lacking enzyme into these cells, outside of the body. To introduce the gene into the cells, a man-made virus (lentiviral vector) is used. The cells are then infused back into the patient, where they are expected to produce and replace the lacking enzyme arylsulfatase A. The replacement of the lacking enzyme is thought to reduce the accumulated sulfatides, thus relieving the symptoms.

At the time of submission of the application for orphan designation, the evaluation of the effects of autologous CD34+ cells transfected with lentiviral vector containing the human arylsulfatase A cDNA in experimental models was ongoing.

At the time of submission of the application for orphan designation, no clinical trials in patients with metachromatic leukodystrophy were initiated.

Autologous CD34+ cells transfected with lentiviral vector containing the human arylsulfatase A cDNA was not authorised anywhere worldwide for the treatment of metachromatic leukodystrophy 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 8 March 2007 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 European Union) 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.