EU/3/20/2297: Orphan designation for the treatment of metachromatic leukodystrophy

Metachromatic leukodystrophy is a hereditary disease caused by the lack of an enzyme called arylsulfatase A. This enzyme is needed to break down substances in the body called sulfatides. Therefore, in patients with the disease, sulfatides gradually build up in the cells of the nervous system and destroy the covering around the nerves called myelin. This causes 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 less than 1 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 52,000 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).

*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, Iceland, Liechtenstein, Norway and the United Kingdom. This represents a population of 519,200,000 (Eurostat 2020).

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. 

The medicine is made of a virus that has been modified to contain genetic material responsible for producing the missing enzyme, arylsulfatase A. The virus is able to cross over from the blood into the brain also from blood into nerve cells. The genetic material is expected to be incorporated into cells in the patient’s body. A single dose of the medicine into a vein is expected to help cells produce arylsulfatase A continually and so reduce symptoms of the disease for a long time.

The type of virus used in this medicine (adeno-associated virus) does not cause disease in humans.

At the time of submission of the application for orphan designation, the evaluation of the effects of the medicine in experimental models was ongoing.

At the time of submission of the application for orphan designation, no clinical trials with the medicine in patients with metachromatic leukodystrophy had been started.

At the time of submission, the medicine was not authorised anywhere in the EU for the treatment of metachromatic leukodystrophy or designated as an orphan medicinal product elsewhere for this condition.

In accordance with Regulation (EC) No 141/2000, the COMP adopted a positive opinion on 20 May 2020, 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.