EU/3/06/369

On 22 May 2006, orphan designation (EU/3/06/369) was granted by the European Commission to Cellerix S.L., Spain, for bilayer engineered skin composed of keratinocytes from the patient (autologous) and fibroblasts from a donor (allogeneic) embedded in a plasma matrix for the treatment of epidermolysis bullosa.
The sponsor changed name to Cellerix S.A. in September 2008.

What is epidermolysis bullosa?

Epidermolysis bullosa describes a group of diseases of the skin and mucous. Patients with epidermolysis bullosa have extremely fragile skin and recurrent blister formation, resulting from minor mechanical friction or injury. Epidermolysis bullosa is caused by defective production of collagen. Collagen is the core substance that makes up the matrix that surrounds cells (extracellular matrix) in the body. It is essential for the support of tissues and gives cells structure from the outside. There are several types of collagen, each with unique function. Epidermolysis bullosa patients have a change in their genetic material (the gene coding for collagen VII has a mutation) and cannot produce collagen VII, a type of collagen essential for the connections of cells of the skin.
There are several forms of hereditary epidermolysis bullosa. Some forms of the condition can be present at birth, while acquired forms occur in adults. Dystrophic epidermolysis bullosa present at birth is characterized by blistering, growing skin and mucous lesions. Adults suffering from the condition may have mitten-like deformities of fingers and toes. Epidermolysis bullosa is chronically debilitating and life-threatening.

What is the estimated number of patients affected by the condition*?

At the time of designation epidermolysis bullosa affected less than 0.5 in 10,000 people in the European Union (EU)*. This is based on the information provided by the sponsor and knowledge of the Committee for Orphan Medicinal Products (COMP). This is below the threshold for orphan designation which is 5 in 10,000. This is equivalent to a total of around 23,000 people.

* Disclaimer: For the purpose of the designation, the number of patients affected by the condition is estimated and assessed based on data from the European Union (EU 25), Norway, Iceland and Liechtenstein. This represents a population of 459,700,000 (Eurostat 2004).

What treatments are available?

At the time of submission of the application for the orphan drug designation there was no treatment authorised in the European Union. Treatment of epidermolysis bullosa included supportive care and antibiotics for the treatment of infections on the skin and, in some cases, surgery.

How is this medicine expected to work?

The bilayer engineered skin composed of keratinocytes (cells from the upper layer of the skin) from the patient (autologous) and fibroblasts (a fibroblast is a type of cell that synthesizes the extracellular matrix that acts as a frame around organs and gives them support) from a donor (allogeneic) embedded in a plasma matrix are expected to provide the missing collagen VII of the skin of patients with epidermolysis bullosa and thus prevent the formation of blisters.

What is the stage of development of this medicine?

The evaluation of the effects of bilayer engineered skin composed of keratinocytes from the patient (autologous) and fibroblasts from a donor (allogeneic) embedded in a plasma matrix in experimental models was ongoing.
At the time of submission of the application for orphan designation, clinical trials in patients with epidermolysis bullosa were ongoing.
Bilayer engineered skin composed of keratinocytes from the patient (autologous) and fibroblasts from a donor (allogeneic) embedded in a plasma matrix was not authorised anywhere worldwide for epidermolysis bullosa or designated as orphan medicinal product elsewhere for this condition, at the time of submission.
According to Regulation (EC) No 141/2000 of 16 December 1999, the Committee for Orphan Medicinal Products (COMP) adopted on 5 April 2006 a positive opinion recommending the grant of the above-mentioned designation.

Opinions on orphan medicinal product designations are based on the following three criteria:

• 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.