EU/3/19/2161: Orphan designation for the treatment of epidermolysis bullosa

Epidermolysis bullosa is a group of inherited diseases 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 reduce life expectancy.
 

At the time of designation, epidermolysis bullosa affected 0.90 in 10,000 people in the European Union (EU). This was equivalent to a total of around 47,000 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 518,400,000 (Eurostat 2019).

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.

Diacerein (taken by mouth) is authorised in some EU countries to treat symptoms of osteoarthritis (swelling and pain in the joints) and other degenerative joint diseases.
Diacerein belongs to a class of substances called anthraquinones. It works by blocking the action of interleukin-1 beta, a protein involved in the inflammation process. Interleukin-1 beta is thought to be over-activated in some patients with epidermolysis bullosa. By blocking its action, diacerein is expected to reduce the inflammation and the number of blisters in patients with the disease.

This medicine is expected to be available as a cream.
 

The effects of diacerein have been evaluated in experimental models.

At the time of submission of the application for orphan designation, no clinical trials with this medicine in patients with epidermolysis bullosa were ongoing.

At the time of submission, this medicine was not authorised anywhere in the EU for the treatment of epidermolysis bullosa or designated as an orphan medicinal product elsewhere for this condition.

In accordance with Regulation (EC) No 141/2000, the COMP adopted a positive opinion on 17 April 2019, 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.