On 7 November 2008, orphan designation (EU/3/08/579) was granted by the European Commission to Chiesi Farmaceutici S.P.A., Italy, for ex vivo expanded autologous human corneal epithelium containing stem cells for the treatment of corneal lesions, with associated corneal (limbal) stem cell deficiency, due to ocular burns.
- What are 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.
- What treatments are available?
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.
- What is the estimated number of patients affected by the condition?
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 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 151,000 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 27), Norway, Iceland and Liechtenstein. This represents a population of 502,282,000 (Eurostat 2008).
- How is this medicine expected to work?
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.
- What is the stage of development of this medicine?
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.
According to Regulation (EC) No 141/2000 of 16 December 1999, the Committee for Orphan Medicinal Products (COMP) adopted a positive opinion on 10 September 2008 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 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.
|Name||Language||First published||Last updated|
|EU/3/08/579: Public summary of positive opinion for orphan designation of ex vivo expanded autologous human corneal epithelium containing stem cells for the treatment of corneal lesions, with associated corneal (limbal) stem cell deficiency, due to ocular burns||(English only)||24/04/2009|
|Active substance||Ex vivo expanded autologous human corneal epithelium containing stem cells|
|Disease/condition||Corneal lesions, with associated corneal (limbal) stem cell deficiency, due to ocular burns|
|Date of decision||06/11/2008|
|Orphan decision number||EU/3/08/579|
Review of designation
During its meeting of 7 to 9 January 2015, the Committee for Orphan Medicinal Products (COMP) reviewed the designation EU/3/08/579 for Holoclar (ex vivo expanded autologous human corneal epithelium containing stem cells) as an orphan medicinal product for the treatment of corneal lesions, with associated corneal (limbal) stem-cell deficiency, due to ocular burns. The COMP assessed whether, at the time of marketing authorisation, the medicinal product still met the criteria for orphan designation. The Committee looked at the seriousness and prevalence of the condition, and the existence of other methods of treatment. As other methods of treatment exist in the European Union (EU), the COMP also considered whether the medicine is of significant benefit to patients with this condition. The COMP recommended that the orphan designation of the medicine be maintained1.
1The maintenance of the orphan designation at time of marketing authorisation would, except in specific situations, give an orphan medicinal product 10 years of market exclusivity in the EU. This means that in the 10 years after its authorisation similar products with a comparable therapeutic indication cannot be placed on the market.
- Life-threatening or long-term debilitating nature of the condition
The Committee for Medicinal Products for Human Use (CHMP) recommended the following indication for Holoclar:
‘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’.
This falls within the scope of the product’s designated orphan indication, which is: ‘treatment of corneal lesions, with associated corneal (limbal) stem cell deficiency, due to ocular burns’.
The COMP concluded that there had been no change in the seriousness of the condition since the orphan designation in 2008. The condition remains debilitating in the long term particularly because it can cause loss of vision.
- Prevalence of the condition
The sponsor provided updated information on the prevalence of the orphan condition based on an extrapolation of data on severe corneal injuries from a survey in the United Kingdom.
On the basis of the information provided by the sponsor and the knowledge of the COMP, the COMP concluded that the prevalence of the orphan condition remains below the ceiling for orphan designation, which is 5 people in 10,000. At the time of the review of the orphan designation, the prevalence was estimated to be less than 0.3 people in 10,000. This is equivalent to a total of fewer than 15,000 people in the EU.
- Existence of other methods of treatment
At the time of the review of the orphan designation, surgical treatments such as corneal transplantations were available to treat corneal lesions in patients with limbal stem-cell deficiency caused by burns.
- Significant benefit of Holoclar
As Holoclar is an autologous product, manufactured from the patient’s own limbal cells, treatment does not carry the same risk of rejection as with some treatments using cells from donors and therefore does not require the use of immunosuppressive medicines.
In addition, Holoclar can be used in patients with only a small amount of undamaged limbal tissue as only a small amount is needed to make the product. In some patients, it can also be used in addition to existing surgical treatments to improve outcomes.
Therefore, although other methods for the treatment of this condition are used in the EU, the COMP concluded that Holoclar is of significant benefit to patients affected by the condition.
Based on the data submitted and the scientific discussion within the COMP, the COMP considered that Holoclar still meets the criteria for designation as an orphan medicinal product and that it should remain in the Community Register of Orphan Medicinal Products.
Sponsor’s contact details
Chiesi Farmaceutici S.p.A
Via Palermo, 26/A
Tel. + 39 0521 2791
Fax + 39 0521 77 41 20
For contact details of patients’ organisations whose activities are targeted at rare diseases, see:
- Orphanet, a database containing information on rare diseases, which includes a directory of patients’ organisations registered in Europe;
- European Organisation for Rare Diseases (EURORDIS), a non-governmental alliance of patient organisations and individuals active in the field of rare diseases.