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Orphan designation

On 8 October 2009, orphan designation (EU/3/09/661) was granted by the European Commission to Lexicon Celtic Ltd, United Kingdom, for (S)-ethyl 2-amino-3-(4-(2-amino-6((R)-1-(4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl)-2,2,2-trifluoroethoxy)pyrimidin-4-yl)phenyl)propanoate for the treatment of carcinoid tumours.

What are carcinoid tumours?

Carcinoid tumours are tumours of the endocrine system that produce hormones. They are slow-growing tumours that usually start in the appendix or in the small bowel. The early symptoms of the disease are mild and depend on where the tumour starts. When the disease gets worse and the tumour becomes metastatic (spreads to other parts of the body), patients develop severe diarrhoea and flushing (reddening of the skin).

Carcinoid tumours are diseases that can cause debilitating symptoms and may be life threatening if they spread to other parts of the body.

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

At the time of designation, carcinoid tumours affected less than 1 in 10,000 people in the European Union (EU)*. This is equivalent to a total of fewer than 50,000 people, and is below the threshold for orphan designation, which is 5 people in 10,000. This is based on the information provided by the sponsor and 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 504,800,000 (Eurostat 2009).

What treatments are available?

Patients with carcinoid tumours can be cured using surgery to remove the tumours if they are found early. In addition, at the time of designation, interferon-alfa was authorised in the EU for the treatment of metastatic carcinoid tumours at later stages of the disease. Somatostatin analogues, such as octreotide and lanreotide, were also used to treat the symptoms caused by the tumours.

The sponsor has provided sufficient information to show that (S)-ethyl 2-amino-3-(4-(2-amino-6((R)-1-(4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl)-2,2,2-trifluoroethoxy)pyrimidin-4-yl)phenyl)propanoate might be of significant benefit for patients with carcinoid tumours because it works in a different way to existing treatments, and because it might reduce the symptoms of the disease in patients who do not respond to existing treatments. In addition, this medicine is to be available as capsules, whereas somatostatin analogues are given by injection. These assumptions will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

How is this medicine expected to work?

Carcinoid tumours produce large amounts of hormones, in particular 5-hydroxytryptamine (5-HT, also known as serotonin), which is thought to be responsible for the symptom of severe diarrhoea in patients with the disease. (S)-ethyl 2-amino-3-(4-(2-amino-6((R)-1-(4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl)-2,2,2-trifluoroethoxy)pyrimidin-4-yl)phenyl)propanoate is expected to work by blocking an enzyme known as tryptophan hydroxylase (TPH), which is responsible for the production of 5-HT. By blocking TPH, this medicine is expected to stop the production of 5-HT, reducing the symptoms of carcinoid tumours.

What is the stage of development of this medicine?

The effects of (S)-ethyl 2-amino-3-(4-(2-amino-6((R)-1-(4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl)-2,2,2-trifluoroethoxy)pyrimidin-4-yl)phenyl)propanoate have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials in healthy volunteers had finished, and trials in patients with carcinoid tumours were planned.

At the time of submission, this medicine was not authorised anywhere in the EU for carcinoid tumours or designated as an orphan medicinal product elsewhere for this condition.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 8 July 2009 recommending the granting of this 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 Community) 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.

Key facts

Product details for <p>(S)-ethyl 2-amino-3-(4-(2-amino-6((R)-1-(4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl)-2,2,2-trifluoroethoxy)pyrimidin-4-yl)phenyl)propanoate</p>
Active substance(S)-ethyl 2-amino-3-(4-(2-amino-6((R)-1-(4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl)-2,2,2-trifluoroethoxy)pyrimidin-4-yl)phenyl)propanoate
Medicine Name
Disease/conditionTreatment of carcinoid tumours
Date of decision08/10/2009
Orphan decision numberEU/3/09/661

Review of designation

Sponsor’s contact details

Lexicon Celtic Limited
16 Charlotte Square
Midlothian EH2 4DF
United Kingdom
Tel. +44 (0)1312 254455
Fax +44 (0)1312 252712

Patients' organisations

For contact details of patients’ organisations whose activities are targeted at rare diseases, see:

  • Orphanet, a database containing information on rare diseases, which includes a directory of patients’ organisations registered in Europe;
  • European Organisation for Rare Diseases (EURORDIS), a non-governmental alliance of patient organisations and individuals active in the field of rare diseases.