EU/3/05/301: Orphan designation for the treatment of shiga-toxin-producing bacterial infection

Shiga-toxin-producing bacterial infection comprises infections caused by bacteria called Shigella dysenteriae type 1 and Escherichia coli. These bacteria can produce a certain poison (shiga toxin). Shiga toxin induces destruction of cell parts needed to produce proteins. Patients get the disease through infected food. As a consequence, these kinds of infections can cause a serious gastrointestinal disease (acute inflammation of the lining of the stomach and the intestines with symptoms such as lack of appetite, nausea, diarrhoea with the presence of blood in the stools and severe abdominal cramps). As a consequence of the infection, the kidneys may be damaged. This is usually accompanied by the destruction of red blood cells (haemolysis) and platelets (cells involved in blood clotting) and called haemolytic uraemia syndrome (HUS). Shiga-toxin-producing bacterial infection is a life-threatening condition.

At the time of designation, shiga-toxin-producing bacterial infection affected approximately 2.1 in 10,000 people in the European Union (EU). This was equivalent to a total of around 98,000 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 25), Norway, Iceland and Liechtenstein. At the time of designation, this represented a population of 466,600,000 (Eurostat 2005).

The current management of the disease consists of supportive treatment, such as the restoration of fluid content to the body that is dehydrated. Several medicinal products were authorised in the Community for treatment of infections caused by Shigella species or E. coli at the time of submission of the application for orphan designation. Satisfactory argumentation has been submitted by the sponsor to justify the assumption that chimeric monoclonal antibody to shiga toxin 1 and 2 might be of potential significant benefit for the treatment of shiga toxin producing bacterial infection because it may offer a new way to fight the disease and it might improve the long-term outcome of the patients. The assumption will have to be confirmed at the time of marketing authorisation. This will be necessary to maintain the orphan status.

Some bacteria have the ability to produce toxins that have a harmful effect on the normal functioning of cells. Chimeric monoclonal antibody to shiga toxin 1 and 2 is expected to neutralise the circulating toxins, thus blocking the direct action of shiga toxin 1 and 2 on the kidneys.

The effects of chimeric monoclonal antibody to shiga toxin 1 and 2 have been evaluated in experimental models.

At the time of submission of the application for orphan designation, no clinical trials in patients with shiga-toxin-producing bacterial infection had been initiated.

Chimeric monoclonal antibody to shiga toxin 1 and 2 was not authorised anywhere worldwide for shiga-toxin-producing bacterial infection or 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 13 July 2005 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.