EU/3/14/1359: Orphan designation for the treatment of mucopolysaccharidosis type I

Mucopolysaccharidosis type I (MPS I) is one of a group of inherited diseases caused by the lack of certain enzymes in lysosomes (structures in the body's cells that break down nutrients and other substances) that are needed to break down substances in the body called glycosaminoglycans (GAGs). In MPS I the enzyme that is lacking is called α-L-iduronidase. Since patients with MPS I cannot break GAGs down properly, they gradually build up in various organs in the body and damage them. This can cause a range of symptoms including impaired vision, developmental delay, mental disability, progressive joint stiffness and skeletal problems, breathing difficulties, enlarged liver and heart disease. The condition varies in severity, with the mildest form known as Scheie syndrome and the most severe as Hurler syndrome.

MPS I is a seriously debilitating and life-threatening disease that leads to multiple disabilities and can result in premature death.

At the time of designation, MPS I affected less than 0.1 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 5,000 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 511,100,000 (Eurostat 2014).

At the time of designation, the medicine Aldurazyme (laronidase) was authorised in the EU to treat the symptoms of MPS I that are not connected with the brain or nerves, by supplying patients with a version of the missing enzyme (enzyme replacement therapy). Some patients were treated with haematopoietic stem cell transplantation, a complex procedure where the patient receives blood stem cells from a matched 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 pentosan polysulfate sodium might be of significant benefit for patients with MPS I because early studies suggest it can provide an alternative treatment to improve symptoms, particularly those affecting the heart and circulation and skeletal symptoms. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

The active substance in this medicine, pentosan polysulfate sodium, is a complex polysaccharide (a molecule built up from sugars) that is believed to reduce the level of GAGs in the body, thus helping to prevent the build-up of GAGs in the tissue of patients with MPS I. In addition, it reduces inflammation and cell damage known as 'oxidative stress'. These actions are expected to relieve the symptoms of the condition.

Pentosan polysulfate sodium has also been used in the treatment of problems caused by blockages in the blood vessels.

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 MPS I had been started.

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

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 9 October 2014 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.