EU/3/09/630: Orphan designation for the treatment of dystrophic epidermolysis bullosa

Dystrophic epidermolysis bullosa is a genetic disease of the skin, in which the outer layer of the skin, the epidermis, separates from the inner layer, the dermis. This makes the skin very fragile and causes severe blistering and scarring. The disease is caused by abnormalities in the COL7A1 gene. This gene is responsible for the production of a protein called 'collagen VII', which normally links the epidermis and the dermis together.

Dystrophic epidermolysis bullosa is a long-term debilitating disease and may be life threatening mainly because of the severe blistering, which results in poor quality of life and shortened life expectancy.

At the time of designation, epidermolysis bullosa affected less than 0.5 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 25,000 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. At the time of designation, this represented a population of 504,800,000 (Eurostat 2009).

At the time of designation, no satisfactory methods were authorised in the EU for the treatment of dystrophic epidermolysis bullosa. Patients were advised to maintain a high standard of personal hygiene and skincare to help blisters heal, avoid infection and protect the skin from damage. Painkillers were also used, and surgery in case of complications.

Skin equivalent graft genetically corrected with a COL7A1-encoding SIN retroviral vector is made up of skin cells taken from the patient, which have been grown in the laboratory to produce a layer of skin for grafting. These cells are modified by a virus so that they have normal copies of the COL7A1 gene inserted in their genes. When the modified skin cells are grafted onto the patient's skin, they are expected to start producing collagen VII, helping the dermis and epidermis to stick together and preventing blister formation. The type of virus used in this medicine ('SIN retrovirus') has been modified so that it does not cause disease in humans.

The evaluation of the effects of this medicine in experimental models is ongoing.

At the time of submission of the application for orphan designation, no clinical trials in patients with dystrophic epidermolysis bullosa had been started.

At the time of submission, this medicine was not authorised anywhere in the EU for dystrophic epidermolysis bullosa or designated as 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 4 March 2009 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 Community) 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.