EU/3/14/1251: Orphan designation for the treatment of glycogen storage disease type II (Pompe's disease)

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 muscles, including the heart muscle and diaphragm (the main breathing muscle under the lungs). The progressive build-up of glycogen causes a wide range of signs and symptoms, including heart problems, breathing difficulties and muscle weakness.

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.

At the time of designation, glycogen storage disease type II affected not more than 1 in 10,000 people in the European Union (EU). This was equivalent to a total of not more than 51,000 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, Myozyme (alglucosidase alfa) 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.

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 in experimental models show that it might improve muscle function of patients with this condition. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

Like Myozyme, this medicine is an enzyme replacement therapy that works by replacing the missing GAA enzyme in patients with glycogen storage disease type II. It is a copy of human GAA, which is produced 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 enzyme. The replacement enzyme helps to break down glycogen and stops its build up in the cells.

The GAA in this medicine is attached to several molecules called 'bismannose-6-phosphate-tetra-mannose glycan'. This is expected to increase the uptake of the enzyme by skeletal muscles (muscles used for movement), thereby improving muscle coordination and strength of patients with glycogen storage disease type II.

The effects of the medicine have been evaluated in experimental models.

At the time of submission of the application for orphan designation, a clinical trial with the medicine in patients withglycogen storage disease type II was ongoing.

At the time of submission, the medicine was not authorised anywhere in the EU for glycogen storage disease type II 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 6 February 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.