EU/3/16/1714: 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 needed to break down substances in the body called glycosaminoglycans (GAGs). In MPS I the enzyme that is lacking is α-L-iduronidase. Since patients with MPS I cannot break GAGs down properly, GAGs 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 long-term debilitating and life-threatening disease that leads to multiple disabilities and can result in premature death.

At the time of designation, MPS I 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 513,700,000 (Eurostat 2016).

At the time of designation, the medicine Aldurazyme (laronidase) was authorised in the EU to treat some of the symptoms of MPS I 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 this medicine might be of significant benefit for patients with MPS I because laboratory studies show that it can restore activity of the missing enzyme without the need for enzyme replacement therapy. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

In most patients with MPS I, the disease is caused by a genetic mutation (change) called a nonsense mutation in the gene for α-L-iduronidase. This mutation prematurely stops production of normal α-L-iduronidase, leading to a shortened enzyme that does not work properly. This medicine is expected to work by enabling the protein-making apparatus in cells to move past the mutation, allowing the cells to produce a functional enzyme, thus easing the symptoms of the disease.

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 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 13 July 2016 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.