EU/3/07/472

Please note that this product was withdrawn from the Community Register of designated orphan medicinal products in November 2012 on request of the sponsor.

On 14 September 2007, orphan designation (EU/3/07/472) was granted by the European Commission to Lux Biosciences GmbH, Germany, for 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} for the treatment of chronic non-infectious uveitis.

What is 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.

What is the estimated number of patients affected by the condition?

Based on the information provided by the sponsor and previous knowledge of the Committee, chronic non-infectious uveitis was considered to affect approximately 4 in 10,000 persons in the European Union*, which, at the time of designation, corresponded to about 202,520 persons in total.

*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).

What treatments are available?

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.

How is this medicine expected to work?

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.

What is the stage of development of this medicine?

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 Committee for Orphan Medicinal Products (COMP) adopted a positive opinion on 25 July 2007 recommending the granting of the abovementioned 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 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.