EU/3/13/1232: Orphan designation for the treatment of epidermolysis bullosa

Epidermolysis bullosa describes a group of diseases of the skin, in which the skin is very fragile and forms severe blisters upon minor mechanical friction or injury. The condition usually is present from birth, although some forms occur in adults. The diseases are caused by abnormalities in the genes responsible for the production of certain proteins that make the skin strong and elastic, such as collagen or keratins.

Epidermolysis bullosa is a long-term debilitating and life-threatening condition because the severe blistering and associated scarring and deformities result in poor quality of life and may also reduce life expectancy.

At the time of designation, epidermolysis bullosa affected less than 0.8 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 41,000 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.
At the time of designation, this represented a population of 512,900,000 (Eurostat 2014).

At the time of designation, no satisfactory methods were authorised in the EU to treat epidermolysis bullosa. A high standard of personal hygiene and skincare were recommended to help blisters heal, to avoid infections and to protect the skin from damage. Painkillers were also used. Surgery was sometimes necessary if there were complications such as deformed hands or the development of skin cancer.

Allantoin has been used for many years in the treatment of wounds and ulcers. It is thought to act by reducing inflammation and stimulating the body's natural mechanisms for removing damaged tissue and encouraging the growth of new replacement tissue. In addition, it may act to prevent the growth of bacteria that can infect damaged areas. In this medicine, these actions could help to heal the blistering associated with epidermolysis bullosa.

The effects of allantoin have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with allantoin in patients with epidermolysis bullosa were ongoing.

At the time of submission, allantoin was not authorised anywhere in the EU for epidermolysis bullosa. Orphan designation of allantoin had been granted in the USA for this condition.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 12 December 2013 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.