EU/3/20/2315: Orphan designation for the treatment of mucopolysaccharidosis VI (Maroteaux-Lamy syndrome)

Mucopolysaccharidosis type VI (also known as Maroteaux-Lamy syndrome) is an inherited disease caused by the lack of an enzyme called arylsulfatase B (ARSB). This enzyme is needed to break down substances in the body called glycosaminoglycans (GAGs). Because the enzyme is not present, GAGs build up in the cells and damage them. This causes a wide range of symptoms, the most noticeable being a short body, a large head, difficulty moving about, clouding of the eyes and hearing loss. The disease is usually diagnosed in children between one and five years of age.

Mucopolysaccharidosis VI is a long-lasting and life-threatening disease because of the damage to various parts of the body, particularly the spine, heart and lungs.

At the time of designation, mucopolysaccharidosis type VI affected approximately 0.01 in 10,000 people in the European Union (EU). This was equivalent to a total of around 500 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, galsulfase was authorised in the EU for the treatment of mucopolysaccharidosis VI. This is an enzyme replacement therapy (ERT) which provides patients with the enzyme they are lacking. Some patients may undergo transplantation to receive haematopoietic (blood) stem cells that are able to produce the missing enzyme.

The sponsor has provided sufficient information to show that pentosan polysulfate sodium might be of significant benefit for patients with mucopolysaccharidosis VI when combined with ERT. Laboratory studies indicate that pentosan polysulfate sodium may improve symptoms not managed by the currently authorised medicine, such as mobility, and preliminary clinical data showed lower levels of GAGs in the urine. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

Pentosan polysulfate sodium is thought to block the effects of inflammatory proteins produced as a result of a build-up of GAGs within the structures of the joint, especially in cartilage. The medicine may also reduce the amount of GAGs in some tissues but it is not understood if this results from reduced production of GAGs or their increased break-down. When used in combination with enzyme replacement therapy, the medicine is expected to reduce inflammation and pain in patients with mucopolysaccharidosis VI.

The effects of pentosan polysulfate sodium have been evaluated in experimental models

At the time of submission of the application for orphan designation, no clinical trials with pentosan polysulfate sodium in patients with mucopolysaccharidosis VI had been started.

Pentosan polysulfate sodium is a well-established substance authorised in the EU for several conditions, including the relief of bladder pain and certain vascular disorders.

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

In accordance with Regulation (EC) No 141/2000, the COMP adopted a positive opinion on 16 July 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.