EU/3/20/2253 - orphan designation for treatment of epidermolysis bullosa

autologous skin equivalent graft composed of keratinocytes and fibroblasts genetically corrected by CRISPR/Cas9-mediated excision of mutation-carrying COL7A1 exon 80

Overview

On 28 February 2020, orphan designation EU/3/20/2253 was granted by the European Commission to Consorcio Centro de Investigación Biomédica en Red, M.P, Spain, for autologous skin equivalent graft composed of keratinocytes and fibroblasts genetically corrected by CRISPR/Cas9-mediated excision of mutation-carrying COL7A1 exon 80 for the treatment of epidermolysis bullosa.

The sponsor's name was updated in November 2022.

What is 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.

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

At the time of designation, epidermolysis bullosa affected less than 0.9 in 10,000 people in the European Union (EU). This was equivalent to fewer than 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).

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^*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 519,200,000 (Eurostat 2020).

 

How is this medicine expected to work?

The medicine is a skin graft containing the patient’s own cells with an abnormal gene ‘edited’ so that the cells can produce a skin protein (called collagen 7) that was previously not produced correctly. The skin graft is expected to behave like healthy skin and no longer form blisters and cause other symptoms of the condition.

The modification of the cells is made using CRISPR-Cas9, a method for editing genes that uses an enzyme combined with a small piece of genetic material (RNA), which allows the precise modification of the abnormal gene (COL7A1).

What is the stage of development of this medicine?

At the time of submission of the application for orphan designation, the evaluation of the effects of the medicine in experimental models was ongoing.

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

At the time of submission, the 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 22 January 2020, recommending the granting of this 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 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.

EU/3/20/2253: Public summary of positive opinion for orphan designation of autologous skin equivalent graft composed of keratinocytes and fibroblasts genetically corrected by CRISPR/Cas9-mediated excision of mutation-carrying COL7A1 exon 80 for the treatm

Reference Number: EMADOC-628903358-1929

Key facts

• Active substance:
  autologous skin equivalent graft composed of keratinocytes and fibroblasts genetically corrected by CRISPR/Cas9-mediated excision of mutation-carrying COL7A1 exon 80
• Intended use:
  Treatment of epidermolysis bullosa
• Orphan designation status:
  Positive
• EU designation number:
  EU/3/20/2253
• Date of designation:
  28/02/2020
• Sponsor:

  Consorcio Centro de Investigación Biomédica en Red;