EU/3/14/1349

On 15 October 2014, orphan designation (EU/3/14/1349) was granted by the European Commission to Voisin Consulting S.A.R.L., France, for recombinant human insulin receptor monoclonal antibody-fused-α-L-iduronidase for the treatment of mucopolysaccharidosis type I.

What is mucopolysaccharidosis type I?

Mucopolysaccharidosis type I is an inherited disease that is caused by the lack of an enzyme called α‑L-iduronidase. This enzyme is needed to break down substances in the body called glycosaminoglycans (GAGs). Since patients with mucopolysaccharidosis type I 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, which may include skeletal deformities, difficulty breathing, problems with the heart, spleen and liver, clouding of the eyes, hearing loss and mental retardation. Without treatment, these symptoms become more severe over time.

Mucopolysaccharidosis type I is a seriously debilitating disease which may be life threatening because it may lead to heart and breathing complication.

What is the estimated number of patients affected by the condition?

At the time of designation, mucopolysaccharidosis type I affected approximately 0.03 in 10,000 people in the European Union (EU). This was equivalent to a total of around 1,500 people*, and is below the ceiling for orphan designation, which is 5 people in 10,000. This isbased on the information provided by the sponsor and the knowledge of the Committee for Orphan Medicinal Products (COMP).

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*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).

What treatments are available?

At the time of designation, the medicine Aldurazyme (laronidase) was authorised in the EU for the treatment of mucopolysaccharidosis type I. This is an ‘enzyme replacement therapy’ which works by providing patients with the enzyme they are lacking. Some patients underwent transplantation to receive haematopoietic (blood) stem cells that are able to produce the missing enzyme.

The sponsor has provided sufficient information to show that this medicine might be of significant benefit for patients with mucopolysaccharidosis type I because preclinical studies have shown that the medicine may reduce accumulation of GAGs in organs and reduce damage to the brain. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

How is this medicine expected to work?

This medicine is expected to work by replacing α‑L-iduronidase, the enzyme that is lacking in mucopolysaccharidosis type I. It is made of α‑L-iduronidase linked to a ‘monoclonal antibody’, a type of protein that has been designed to recognise and attach to insulin receptors found on cells throughout the body. Insulin receptors are also located in the blood-brain barrier that separates the bloodstreams from the brain. Once attached to insulin receptors, the medicine is expected to be carried inside the cells in the body and also across the blood-brain barrier into the brain tissue, where the α‑L-iduronidase will replace the missing enzyme. The replacement enzyme is expected to help break down GAGs and stop them accumulating in the various tissues, including the brain, thereby relieving the symptoms of the disease.

The medicine is made by a method known as ‘recombinant DNA technology’: it is made by cells into which a gene (DNA) has been introduced that makes them able to produce the medicine.

What is the stage of development of this medicine?

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 I had been started.

At the time of submission, the medicine was not authorised anywhere in the EU for mucopolysaccharidosis type I. 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 4 September 2014 recommending the granting of this designation.

Opinions on orphan medicinal product designations are based on the following three criteria:

• 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.

The Committee for Orphan Medicinal Products reviews the orphan designation of a product if it is approved for marketing authorisation.