EU/3/07/472: Orphan designation for the treatment of chronic non-infectious uveitis

Uveitis means inflammation of the uvea, the middle layer of the eye. This can be due to an infection by a foreign organism, such as bacteria, or caused by an auto-immune reaction (the body's own defence system attacking normal tissue). Most cases of uveitis are however idiopathic, which means that the cause is unknown.

Uveitis can affect one eye or both eyes and may cause varying degrees of discomfort or pain, with or without blurring of vision. Chronic non-infectious uveitis is chronically debilitating, in particular because it may increases the risk of visual impairment and subsequent blindness.

At the time of designation, chronic non-infectious uveitis affected approximately 4 in 10,000 people in the European Union (EU). This was equivalent to a total of around 200,000 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 500,300,000 (Eurostat 2007).

Several medicinal products were available for the treatment of chronic non-infectious uveitis and were authorised in some Member States in the Community at the time of submission of the application for orphan drug designation. Most treatments aim to suppress (weaken) the response of the immune system, the body's natural defence system, thus relieving the inflammation.

Satisfactory argumentation has been submitted by the sponsor to justify the assumption that cyclo {{(E,Z)-(2S,3R,4R)-3-hydroxy-4-methyl-2-(methylamino)nona-6,8-dienoyl}-L-2-aminobutyryl-N-methyl-glycyl-N-methyl-L-leucyl-L-valyl-N-methyl-L-leucyl-L-alanyl-D-alanyl-N-methyl-L-leucyl-N-methyl-L-leucyl-N-methyl-L-valyl} might be of potential significant benefit for the treatment of chronic non-infectious uveitis, mainly because it may provide a major contribution to patient care. This assumption will have to be confirmed at the time of marketing authorisation. This will be necessary to maintain the orphan status.

The mechanism of action of cyclo {{(E,Z)-(2S,3R,4R)-3-hydroxy-4-methyl-2-(methylamino)nona-6,8-dienoyl}-L-2-aminobutyryl-N-methyl-glycyl-N-methyl-L-leucyl-L-valyl-N-methyl-L-leucyl-L-alanyl-D-alanyl-N-methyl-L-leucyl-N-methyl-L-leucyl-N-methyl-L-valyl} is to suppress (weaken) the immune system by targeting especially the so called T-lymphocytes, a type of white blood cells that are particularly active in inflammation. According to the sponsor, this is thought to decrease the inflammation and thus the symptoms of chronic non-infectious uveitis.

The effects of cyclo {{(E,Z)-(2S,3R,4R)-3-hydroxy-4-methyl-2-(methylamino)nona-6,8-dienoyl}-L-2-aminobutyryl-N-methyl-glycyl-N-methyl-L-leucyl-L-valyl-N-methyl-L-leucyl-L-alanyl-D-alanyl-N-methyl-L-leucyl-N-methyl-L-leucyl-N-methyl-L-valyl} have been evaluated in experimental models.

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

Cyclo {{(E,Z)-(2S,3R,4R)-3-hydroxy-4-methyl-2-(methylamino)nona-6,8-dienoyl}-L-2-aminobutyryl-N-methyl-glycyl-N-methyl-L-leucyl-L-valyl-N-methyl-L-leucyl-L-alanyl-D-alanyl-N-methyl-L-leucyl-N-methyl-L-leucyl-N-methyl-L-valyl} was not authorised anywhere worldwide for the treatment of non-infectious uveitis nor designated as an 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 25 July 2007 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.