EU/3/19/2140

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).

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 II, with early studies suggesting that this medicine may reduce GAGs build-up in different tissues and organs, including the brain, while the authorised medicine does not reach the brain. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

This medicine works by replacing the enzyme that is missing or defective in patients with mucopolysaccharidosis type II, iduronate-2-sulfatase. The medicine comprises of two parts: the missing enzyme and a monoclonal antibody (a type of protein) which allows the medicine to reach the brain. The monoclonal antibody is designed to attach to a target on the blood-brain barrier, which separates the blood from the brain tissue. By replacing the missing enzyme, the medicine is expected to improve the symptoms of the disease, including symptoms affecting the brain.

The effects of the medicine have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with the medicine in patients with mucopolysaccharidosis type II were ongoing in Japan and Brazil.

At the time of submission, the medicine was not authorised anywhere in the EU for treatment of 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 24 January 2019 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.