EU/3/01/077: Orphan designation for the treatment of short bowel syndrome

Some diseases of the gastrointestinal tract (the stomach and the intestines) have to be treated through the surgical removal of a part of the small intestines. In many patients this procedure leads to subsequent short-bowel syndrome. The small intestine (the bowel) is the organ that food passes through from the stomach and it is where it is degraded (mainly in the first part, the jejunum) and absorbed through the walls of the intestines (mainly in the lower part, the ileum). Depending on which part of the bowel is removed, different symptoms may occur, such as diarrhoea, dehydration, malabsorption leading to progressive malnutrition associated with fatty-acid and vitamin deficiencies, anaemia (blood deficiency), and weight loss. In children, this is typically accompanied by delayed growth. Short-bowel syndrome is chronically debilitating.

At the time of designation, short bowel syndrome affected not more than 0.35 in 10,000 people in the European Union (EU). This was equivalent to a total of not more than 13,000 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 509,000,000 (Eurostat 2013).

There were no authorised medicines for the treatment of short-bowel syndrome in the Community at the time of submission of application for orphan drug designation. Many patients with the syndrome are treated with total or supplemental parenteral nutrition (receiving food intravenously).

[Gly2]-recombinant human glucagon-like peptide is a protein that is structurally similar to a natural protein called glucagon-like peptide 2 which is produced by cells in the lower part of the intestines. This substance acts as a signalling molecule and when it binds to its receptors it can stimulate various reactions and processes in the tissue. One of the effects is thought to be an increase in proliferation and decrease in cell death as well as improving the absorptive qualities of the small intestine. Thus, [gly2]-recombinant human glucagon-like peptide is expected to improve the function of the remaining part of the intestine.

The effects of [gly2]-recombinant human glucagon-like peptide were evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials in patients with short bowel syndrome were ongoing.

[gly2]-recombinant human glucagon-like peptide was not authorised anywhere worldwide for short bowel syndrome, at the time of submission.

Orphan designation of [gly2]-recombinant human glucagon-like peptide was granted in the United States for this condition.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 26 October 2001 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.