EU/3/17/1835: Orphan designation for the treatment of epidermolysis bullosa

Epidermolysis bullosa is a group of inherited diseases of the skin, in which the skin is very fragile and forms severe blisters after even minor friction (rubbing) or injury. In most cases, symptoms of epidermolysis bullosa appear from birth, but for some forms, symptoms may not occur until adulthood. The diseases are caused by mutations (changes) 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 approximately 0.6 in 10,000 people in the European Union (EU). This was equivalent to a total of around 31,000 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 515,700,000 (Eurostat 2017).

At the time of designation, no satisfactory methods were authorised in the EU to treat epidermolysis bullosa. Good 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 for complications such as deformed hands or the development of skin cancer.

This medicine is prepared individually for patients who have epidermolysis bullosa due to mutations in the COL7A1 gene. This gene normally produces a substance called collagen 7 that helps hold skin layers together. The medicine consists of patient's own skin cells called keratinocytes, which are modified in the laboratory with a virus that has been engineered to transfer the normal COL7A1 gene into the cells. The modified cells are grown in a layer to make a skin graft that can be surgically transplanted back to the patient. The modified skin cells are then expected to grow normally and produce collagen 7, correcting the cause of the condition, improving blister healing and preventing blister formation.

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 this medicine in patients with epidermolysis bullosa were ongoing.

At the time of submission, the medicine was not authorised anywhere in the EU for epidermolysis bullosa 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 19 January 2017 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.