EU/3/01/077

On 11 December 2001, orphan designation (EU/3/01/077) was granted by the European Commission to Pharm Research Associates (UK) Ltd, United Kingdom, for [gly2]-recombinant human glucagon-like peptide for the treatment of short-bowel syndrome.

The sponsorship was transferred to Parexel International Limited, United Kingdom in November 2002 and subsequently to Nycomed Danmark ApS, Denmark in April 2008.

What is 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.

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

At the time of designation short-bowel syndrome affected not more than 0.35 in 10,000 people in the European Union (EU)*. This is based on the information provided by the sponsor and knowledge of the Committee for Orphan Medicinal Products (COMP). This is below the threshold for orphan designation which is 5 in 10,000. This is equivalent to a total of around 13,000 people.

*Disclaimer: For the purpose of the designation, the number of patients affected by the condition is estimated and assessed based on data from the European Union. This represents a population of 377,000,000 (Eurostat 2001).

What treatments are available?

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).

How is this medicine expected to work?

[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.

What is the stage of development of this medicine?

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.

According to Regulation (EC) No 141/2000 of 16 December 1999, the Committee for Orphan Medicinal Products (COMP) adopted a positive opinion on 26 October 2001 recommending the granting of the above-mentioned 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;
• and either the rarity of the condition (affecting not more than five in 10,000 people in the Community) or the 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 the quality, safety and efficacy is necessary before a product can be granted a marketing authorisation.

During its meeting of 10-11 July 2012, the Committee for Orphan Medicinal Products (COMP) reviewed the designation EU/3/01/077 for Revestive (teduglutide)¹ as an orphan medicinal product for the treatment of short-bowel syndrome. The COMP assessed whether, at the time of marketing authorisation, the medicinal product still met the criteria for orphan designation. The Committee looked at the seriousness and prevalence of the condition, and the existence of other satisfactory methods of treatment. The COMP recommended that the orphan designation of the medicine be maintained².

¹ At time of orphan designation teduglutide was known as [gly2]-recombinant human glucagon-like peptide.
² The maintenance of the orphan designation at time of marketing authorisation would, except in specific situations, give an orphan medicinal product 10 years of market exclusivity in the European Union (EU). This means that in the 10 years after its authorisation, similar products with a comparable therapeutic indication cannot be placed on the market.

Life-threatening or long-term debilitating nature of the condition

The Committee for Medicinal Products for Human Use (CHMP) recommended the authorisation of Revestive for:

treatment of adult patients with short-bowel syndrome. Patients should be stable following a period of intestinal adaptation after surgery.

This falls within the scope of the product’s designated orphan indication, which is: ‘treatment of short-bowel syndrome’.

The COMP concluded that there had been no change in the seriousness of the condition since the orphan designation in 2001. Short-bowel syndrome remains a condition that is serious, debilitating in the long term and, in many cases, life-threatening, particularly because it may lead to severe malnutrition, generalised infections or metabolic problems, as well as liver failure.

Prevalence of the condition

The sponsor provided estimates on the prevalence of short-bowel syndrome from the scientific literature and data from a registry in Sweden.

On the basis of the information provided by the sponsor and the knowledge of the COMP, the COMP concluded that the prevalence of short-bowel syndrome remains below the ceiling for orphan designation, which is 5 people in 10,000. At the time of the review of the orphan designation, the prevalence was estimated to be less than 0.44 people in 10,000. This is equivalent to a total of fewer than 22,300 people in the EU.

Existence of other satisfactory methods of treatment

The COMP noted that, at the time of the review of the orphan designation, no medicinal products were authorised in the EU for patients with short-bowel syndrome. Treatments aimed at relieving the symptoms of the condition, including dietary measures and parenteral nutrition, and were not considered satisfactory.

Conclusions

Based on the data submitted and the scientific discussion within the COMP, the COMP considered that Revestive still meets the criteria for designation as an orphan medicinal product and that it should remain in the Community Register of Orphan Medicinal Products.