EU/3/11/898: Orphan designation for the treatment of chronic non-infectious uveitis

Uveitis is inflammation of the uvea, the middle layer of the eye. The inflammation can affect one or both eyes, and may cause discomfort, pain, and blurring of vision. Non-infectious uveitis is usually caused by the body's immune system (the body's natural defences) attacking normal tissue and not by an infection.

Chronic (long-term) non-infectious uveitis is a long-term debilitating disease because it may lead to partial or complete loss of vision (blindness).

At the time of designation, chronic non-infectious uveitis affected approximately 4.1 in 10,000 people in the European Union (EU)*. This is equivalent to a total of around 208,000 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. This represents a population of 506,300,000 (Eurostat 2011).

At the time of designation, several medicines were authorised in Member States of the EU for the treatment of non-infectious uveitis. The first treatment option was corticosteroids, which were used to reduce the inflammation by lowering the activity of the immune system. Other immunosuppressant agents such as ciclosporin and azathioprine were also authorised for use in chronic non-infectious uveitis.

The sponsor has provided sufficient information to show that sirolimus might be of significant benefit for patients with chronic non-infectious uveitis because it works in a different way to existing treatments and can be administered locally, as seen in early studies. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

Sirolimus is an immunosuppressive agent, which has been used for several years to prevent organ rejection following a transplant. It is expected to work by blocking an enzyme called 'mammalian target of rapamycin' (mTOR). In the body, sirolimus first attaches to a protein called FKBP-12 that is found inside cells to make a 'complex' which then blocks mTOR. Since mTOR is involved in the activation and proliferation of T lymphocytes (white blood cells that play a role in inflammation), sirolimus is expected to reduce the inflammation in chronic non-infectious uveitis. Sirolimus also stops the production of growth factors and genes involved in uveitis. Sirolimus is expected to be injected into or around the eye.

The effects of sirolimus have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with sirolimus in patients with chronic non-infectious uveitis were ongoing.

At the time of submission, sirolimus was not authorised anywhere in the EU for chronic non-infectious uveitis or designated as an 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 10 June 2011 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 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.