EU/3/08/579: Orphan designation for the corneal lesions, with associated corneal (limbal) stem cell deficiency, due to ocular burns

Corneal lesions are areas of damage to the cornea, the transparent surface at the front of the eye in front of the pupil. The surface of the cornea is constantly being renewed and replaced by the production of new cells that are produced by 'stem cells' in the lower layers of the cornea, called the 'basal limbal epithelium'. Ocular burns (burns to the eye) because of chemicals or heat can damage these stem cells. This can cause a deficiency (low number) of the stem cells, reducing the renewal and replacement of the surface of the cornea. This results in the cornea being repaired by different types of eye cell, which can make the cornea opaque and impair the patient's vision.

This condition is considered to be debilitating because of loss of vision.

At the time of designation, corneal lesions, with associated corneal (limbal) stem cell deficiency, due to ocular burns affected approximately 0.3 in 10,000 people in the European Union (EU). This was equivalent to a total of around 15,000 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 27), Norway, Iceland and Liechtenstein. At the time of designation, this represented a population of 502,800,000 (Eurostat 2008)).

There are no authorised products for this condition in the Community, although surgery, such as transplanting a cornea from a donor who has recently died, can been used. Although this can restore the patient's vision, failure of the cornea can occur at any time after the transplant.

Ex vivo expanded autologous human corneal epithelium containing stem cells could be of potential significant benefit for the treatment of corneal lesions, with associated corneal (limbal) stem cell deficiency, due to ocular burns, because they might act differently from other methods. This assumption will have to be confirmed at the time of marketing authorisation. This will be necessary to maintain the orphan status.

This product is made of a small sample of cells that are taken from an undamaged part of the basal limbal epithelium in the patient's cornea. The cells are attached to a 'glue' made of chemically-modified fibrin and grown in the laboratory to produce a replacement surface (epithelium) for the cornea. The epithelium is then implanted into the patient's damaged eye or eyes. The stem cells contained within the epithelium then help the cornea to regenerate, restoring the patient's vision.

The effects of this product have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials in patients with corneal lesions, with associated corneal (limbal) stem cell deficiency, due to ocular burns were ongoing.

At the time of submission, this product was not authorised anywhere worldwide for this condition or designated as orphan medicinal product elsewhere for this condition at the time of submission.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 10 September 2008 recommending the granting of this designation.

Update: ex vivo expanded autologous human corneal epithelium containing stem cells (Holoclar) has been authorised in the EU since 17 February 2015 for treatment of adult patients with moderate to severe limbal stem cell deficiency (defined by the presence of superficial corneal neovascularisation in at least two corneal quadrants, with central corneal involvement, and severely impaired visual acuity), unilateral or bilateral, due to physical or chemical ocular burns. A minimum of 1-2 mm² of undamaged limbus is required for biopsy.

• 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.