EU/3/10/752: Orphan designation for the treatment of Gaucher disease

Gaucher disease is an inherited disorder that is caused by the lack of an enzyme called glucocerebrosidase. This enzyme normally breaks down a fatty waste product called glucocerebroside. Without the enzyme, glucocerebroside builds up in the body, typically in the liver, spleen and bone marrow. This causes a wide range of symptoms, including anaemia (low red blood cell counts), tiredness, easy bruising and a tendency to bleed, an enlarged spleen and liver, and bone pain and fractures.

Gaucher disease is a long-term, debilitating and life-threatening disease that is associated with a reduced life expectancy if left untreated.

At the time of designation, Gaucher disease affected approximately 0.3 in 10,000 people in the European Union (EU)*. This is equivalent to a total of around 15,000 people, and is below the threshold 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 506,500,000 (Eurostat 2010).

At the time of designation, two medicines, imiglucerase and miglustat, were authorised for the treatment of Gaucher disease in the EU. Imiglucerase is an 'enzyme replacement therapy' that works by replacing the missing enzyme. Miglustat blocks the production of glucocerebroside and is used in patients who cannot receive enzyme replacement therapy.

The sponsor has provided sufficient information to show that velaglucerase alfa might be of significant benefit for patients with Gaucher disease because it may represent an alternative treatment to imiglucerase, should the long-term supply problems that are occurring with this medicine continue or happen again in the future. Velaglucerase alfa might also be less 'immunogenic' than imiglucerase. This means that it might be less likely to trigger the production of antibodies (proteins that are produced in response to a substance, which can reduce the effects of a treatment). These assumptions will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

Velaglucerase alfa is an enzyme replacement therapy that is expected to work by replacing the missing enzyme in Gaucher disease, helping to break down glucocerebroside and stopping it building up in the body. Velaglucerase alfa is produced by a method known as 'recombinant DNA technology': it is made by human cells that have received a gene (DNA), which make them able to produce the enzyme.

The effects of velaglucerase alfa have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with velaglucerase alfa in patients with Gaucher disease were ongoing.

At the time of submission, velaglucerase alfa was authorised and had been granted orphan designation in the United States of America for Gaucher disease.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 3 March 2010 recommending the granting of this designation.

Update: Velaglucerase alfa (Vpriv) was authorised in the EU on 26 August 2010 for for long-term enzyme replacement therapy (ERT) in patients with type 1 Gaucher disease.

• 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.