EU/3/17/1956: Orphan designation for the treatment of mucopolysaccharidosis type II (Hunter's syndrome)

Mucopolysaccharidosis type II (also known as Hunter's syndrome) is an inherited disease that is caused by the lack of an enzyme called iduronate-2-sulfatase. This enzyme is needed to break down substances in the body called glycosaminoglycans (GAGs). Since patients with mucopolysaccharidosis type II cannot break these substances down, the GAGs gradually build up in most of the organs in the body and damage them. This causes a wide range of symptoms, particularly difficulty breathing, difficulty walking, mental disability and behavioural problems. Without treatment, these symptoms become more severe over time.

Mucopolysaccharidosis type II primarily affects male patients. It is a seriously debilitating and life-threatening disease that leads to mental disability and death during youth.

At the time of designation, mucopolysaccharidosis type II affected approximately 0.02 in 10,000 people in the European Union (EU). This was equivalent to a total of around 1,000 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).

*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 28), Norway, Iceland and Liechtenstein. This represents a population of 515,700,000 (Eurostat 2017).

At the time of designation, the medicine Elaprase (idursulfase) was authorised in the EU for the treatment of mucopolysaccharidosis type II. This is an enzyme replacement therapy which works by replacing the enzyme that patients are lacking. Some patients were treated with haematopoietic stem cell transplantation, a procedure where the patient's bone marrow is replaced by stem cells from a donor; the stem cells are able to develop into normal blood cells that can produce the missing enzyme.

The sponsor has provided sufficient information to show that the medicine might be of significant benefit for patients with mucopolysaccharidosis type II because laboratory studies indicate that it may slow down the worsening of the patient's mental functions. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

This medicine is made of a virus containing the gene for the iduronate-2-sulfatase enzyme, which is lacking in patients with mucopolysaccharidosis type II. When given to the patient, the virus is expected to carry the gene into the liver cells, enabling these cells to start producing the enzyme. The enzyme is then expected to enter the blood and be taken up by cells in various other organs, including the brain. As a result, the cells will be able to break down the GAGs, thereby helping to relieve symptoms of the disease.

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

The effects of the medicine 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 mucopolysaccharidosis type II had been started.

At the time of submission, the medicine was not authorised anywhere in the EU for mucopolysaccharidosis type II. Orphan designation of the medicine had been granted in the United States for this condition.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 7 December 2017 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.