EU/3/09/651: Orphan designation for the treatment of atopic keratoconjunctivitis

Atopic keratoconjunctivitis is long-term inflammation of the eye that can occur in patients with atopic dermatitis (eczema). It causes the skin of the eyelids to become red and scaly, and to weep fluid. The conjunctiva (the membrane lining the eyelid and covering the eyeball) may also become swollen and red, sometimes with a discharge of clear fluid or pus. The inflammation can also affect the cornea (the transparent surface at the front of the eye that covers the iris and the pupil). Patients with this disease have itchy, painful eyes and blurred vision, and are oversensitive to light.
Atopic keratoconjunctivitis is a long-term debilitating disease because it may lead to eye infections and blindness.

At the time of designation, atopic keratoconjunctivitis affected approximately 1.5 in 10,000 people in the European Union (EU)*. This is equivalent to a total of around 76,000 people, and is below the threshold for orphan designation, which is 5 people in 10,000. This is based on the information provided by the sponsor and 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. This represents a population of 504,800,000 (Eurostat 2009).

At the time of submission of the application for orphan designation, several medicines were available in the EU for the treatment of atopic keratoconjunctivitis, including anti-inflammatory medicines such as corticosteroids and anti-allergic medicines such as antihistamines.
The sponsor has provided sufficient information to show that ciclosporin (eye drops, solution) might be of significant benefit for patients with atopic keratoconjunctivitis because early studies have shown that by giving this medicine locally into the eye it might have fewer side effects than existing treatments. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

Ciclosporin is an immunosuppressant medicine (a medicine that reduces the activity of the immune system) that has been used since the early 1980s. Ciclosporin (eye drops, solution) is a new formulation of ciclosporin that is to be given as eye drops. In atopic keratoconjunctivitis, this medicine is expected to reduce inflammation of the eye by reducing the production of immune cells called 'lymphocytes'.

The effects of ciclosporin (eye drops, solution) have been evaluated in experimental models.
At the time of submission of the application for orphan designation, a clinical trial in healthy volunteers had finished, and additional studies in patients with atopic keratoconjunctivitis were planned.
At the time of submission, ciclosporin (eye drops, solution) was not authorised anywhere in the EU for atopic keratoconjunctivitis or designated as orphan medicinal product elsewhere for this condition.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 4 June 2009 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 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.