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Orphan designation

On 4 July 2012, orphan designation (EU/3/12/1018) was granted by the European Commission to TMC Pharma Services Ltd, United Kingdom, for recombinant adeno-associated viral vector containing human acid alfa-glucosidase-gene for the treatment of glycogen storage disease type II (Pompe's disease).

The sponsorship was transferred to Audentes Therapeutics UK Limited, United Kingdom, in January 2016.

What is glycogen storage disease type II?

Glycogen storage disease type II, also known as Pompe’s disease, is an inherited disorder that is caused by the lack of an enzyme called acid alpha glucosidase (GAA). This enzyme is contained in lysosomes (part of the body’s cells that break down nutrients and other materials). GAA breaks down glycogen (a complex sugar stored in the body) into glucose. When this enzyme is lacking, large amounts of glycogen build up in the body, typically in the muscle cells controlling breathing or the contraction of the heart, which causes damage to these cells. Glycogen also builds up in some specialised nerve cells called motor neurons, which control the movement of muscles in the body.

Glycogen storage disease type II is a long-term debilitating and life-threatening disease because it causes breathing and heart problems and is associated with premature death.

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

At the time of designation, Glycogen storage disease type II affected between 0.6 and 3.8 in 10,000 people in the European Union (EU)*. This is equivalent to a total of between 30,000 and 192,000 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 27), Norway, Iceland and Liechtenstein. This represents a population of 506,300,000 (Eurostat 2011).

What treatments are available?

At the time of designation, Myozyme (human recombinant alglucosidase alpha enzyme) was authorised for the treatment of glycogen storage disease type II in the EU. Myozyme is an ‘enzyme replacement therapy’ that works by replacing the missing GAA enzyme. In addition, antibiotics and anti-inflammatories are used to manage the symptoms of the disease.

The sponsor has provided sufficient information to show that this medicine might be of significant benefit for patients with glycogen storage disease type II because early studies suggest that the medicine may provide long-term correction of the cause of the disease, potentially leading to a reduction in hospital admissions and need for respiratory support. In addition, it may also reach motor neurones, unlike existing treatment. These assumptions 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?

Glycogen storage disease type II is caused by defects in the gene GAA, which is responsible for the production of the GAA enzyme. This medicine is made up of a virus that contains normal copies of the GAA gene. When injected into the patient’s muscles, it is expected that the virus will carry the GAA gene into the body’s cells where it will produce the GAA enzyme. This is expected to replace the missing GAA enzyme, which will enable cells to break down glycogen correctly, thereby preventing its build up and damage to muscle and nerve cells.

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 glycogen storage disease type II were ongoing.

At the time of submission, the medicine was not authorised anywhere in the EU for glycogen storage disease type II. Orphan designation of the medicine had been granted in the United States of America for this condition.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 21 May 2012 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.

Key facts

Product details for <p>Recombinant adeno-associated viral vector containing human acid alfa-glucosidase-gene</p>
Active substanceRecombinant adeno-associated viral vector containing human acid alfa-glucosidase-gene
Medicine Name
Disease/conditionTreatment of glycogen storage disease type II (Pompe's disease)
Date of decision04/07/2012
Orphan decision numberEU/3/12/1018

Review of designation

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

Sponsor’s contact details

Audentes Therapeutics UK Limited
c/o Hackwood Secretaries Limited
One Silk Street
London EC2Y 8HQ
United Kingdom
Tel. +44 (0)20 7456 2000
Fax +44 (0)20 7456 2222

Patients' organisations

For contact details of patients’ organisations whose activities are targeted at rare diseases see:

  • Orphanet, a database containing information on rare diseases which includes a directory of patients’ organisations registered in Europe;
  • European Organisation for Rare Diseases (EURORDIS), a non-governmental alliance of patient organisations and individuals active in the field of rare diseases.