EU/3/18/2039 - orphan designation for treatment of mucopolysaccharidosis type I

recombinant adeno-associated viral vector serotype 9 containing human iduronidase gene

Overview

On 27 June 2018, orphan designation (EU/3/18/2039) was granted by the European Commission to REGENXBIO EU Limited, Ireland, for recombinant adeno-associated viral vector serotype 9 containing human iduronidase gene (also known as RGX-111) for the treatment of mucopolysaccharidosis type I.

What is mucopolysaccharidosis type I?

Mucopolysaccharidosis type I is an inherited disease caused by the lack of an enzyme called alpha-L-iduronidase. This enzyme is needed to break down substances in the body called glycosaminoglycans (GAGs). Since patients with mucopolysaccharidosis type I cannot break down GAGs properly, GAGs 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, 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.

Mucopolysaccharidosis type I is a long-term debilitating and life-threatening disease that leads to multiple disabilities and can result in premature death.

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 is based 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 517,400,000 (Eurostat 2018).

What treatments are available?

At the time of designation, the medicine Aldurazyme (laronidase) was authorised in the EU to treat some of the physical (non-mental) symptoms of mucopolysaccharidosis type I by replacing the missing enzyme (enzyme replacement therapy). 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 type I because laboratory studies indicate that it may improve the mental symptoms of the condition. 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 made of a virus containing the gene for the alpha-L-iduronidase enzyme, which is lacking in patients with mucopolysaccharidosis type I. When injected into the patient's spine, the virus is expected to carry the gene into nerve cells in the spine and brain, enabling them to start producing the enzyme. As a result, the cells will be able to break down GAGs and so help to relieve symptoms of the disease. The virus may also enter the blood to some extent and be taken up by cells in other organs in the body. It is expected that a single injection will have long-term beneficial effect.

The type of virus used in this medicine ('adeno-associated virus') does not cause disease in humans.

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, clinical trials with the medicine in patients with mucopolysaccharidosis type I were ongoing.

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 mucopolysaccharidosis type I.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 24 May 2018 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.

EU/3/18/2039: Public summary of opinion on orphan designation: Recombinant adeno-associated viral vector serotype 9 containing human iduronidase gene for the treatment of mucopolysaccharidosis type I

Reference Number: EMA/373289/2018

Key facts

• Active substance:
  recombinant adeno-associated viral vector serotype 9 containing human iduronidase gene
• Intended use:
  Treatment of mucopolysaccharidosis type I
• Orphan designation status:
  Positive
• EU designation number:
  EU/3/18/2039
• Date of designation:
  27/06/2018
• Sponsor:

  REGENXBIO EU Limited; 25-28 North Wall Quay; Dublin 1 D01H104; Ireland; Tel. [phone]; E-mail: [e-mail];

Review of designation

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