EU/3/10/813: Orphan designation for the treatment of metachromatic leukodystrophy

Metachromatic leukodystrophy is a hereditary disease that is caused by the lack of an enzyme called arylsulfatase A. This enzyme is needed to break down substances in the body called sulfatides. As patients with the disease cannot break sulfatides down, sulfatides gradually build up in the cells of the nervous system and destroy the sheath around the nerves. This causes a wide range of symptoms, such as muscle wasting and paralysis, progressive loss of vision, seizures (fits) and dementia (loss of intellectual function).

Metachromatic leukodystrophy is a seriously debilitating and life-threatening disease because the symptoms get worse over time, leading to severe disability and death usually in adolescence.

At the time of designation, metachromatic leukodystrophy affected approximately 0.01 in 10,000 people in the European Union (EU)*. This is equivalent to a total of around 500 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. This represents a population of 506,500,000 (Eurostat 2010).

At the time of designation, no satisfactory methods were authorised in the EU for the treatment of metachromatic leukodystrophy. Patients received supportive treatment to temporarily relieve the symptoms of the disease, such as physiotherapy and antiepileptic medicines. In a minority of cases, haematopoietic stem-cell transplantation was used (a complex procedure where the patient receives stem cells to help restore the bone marrow).

Recombinant human arylsulfatase A is expected to work in the same way as the human arylsulfatase A, which is missing in patients with metachromatic leukodystrophy. The replacement enzyme is expected to help break down sulfatides and stop them accumulating in the nervous system, thereby relieving the symptoms of the disease.

The medicine is made by a method known as 'recombinant DNA technology': it is made by human cells that have received a gene (DNA) that makes them able to produce arylsulfatase A.

The effects of a similar medicine derived from hamster cells have been evaluated in experimental models.

At the time of submission of the orphan designation application, no clinical trials with recombinant human arylsulfatase A in patients with metachromatic leukodystrophy had been started.

At the time of submission, recombinant human arylsulfatase A was not authorised anywhere in the EU for metachromatic leukodystrophy. Orphan designation of this medicine had been granted in the United States of America for metachromatic leukodystrophy.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 9 September 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.