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Orphan designation

On 27 February 2009, orphan designation (EU/3/09/614) was granted by the European Commission to Exelgyn, France, for mifepristone for the treatment of endogenous hypercortisolism (Cushing’s syndrome).

What is endogenous hypercortisolism (Cushing’s syndrome)?

Hypercortisolism (Cushing’s syndrome) is a set of symptoms caused by an excess of the hormone cortisol in the blood. The symptoms include weight gain (particularly in the face and neck), easy bruising, excessive growth of coarse hair on the face, weakening of the muscles and bones, and high blood pressure. ‘Endogenous’ means that the excess cortisol is caused by the body producing too much of the hormone and not by the patient taking medicines that can cause the condition. Endogenous hypercortisolism is usually caused by a tumour of the glands that are involved in the production of cortisol.

Endogenous hypercortisolism is a severe disease that is long lasting and may be life threatening because of its complications, including diabetes, high blood pressure and mental problems.

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

At the time of designation, endogenous hypercortisolism affected around 0.6 in 10,000 people in the European Union (EU)*. This is below the threshold for orphan designation, which is 5 in 10,000, and is equivalent to a total of around 30,000 people. 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 504,800,000 (Eurostat 2009).

What treatments are available?

At the time of designation, the main treatments for endogenous hypercortisolism involved treating the tumour responsible for causing the high cortisol levels, such as by surgery or radiotherapy (treatment with radiation) and using medicines to block the production of cortisol.

The sponsor has provided sufficient information to show that mifepristone might be of potential significant benefit for the patients because it works in a different way to the other medicines used in endogenous hypercortisolism and because it could be an alternative treatment for the condition. This assumption 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?

Mifepristone has several medical uses. In endogenous hypercortisolism, mifepristone is expected to act as a ‘glucocorticoid receptor antagonist’. This means that it blocks the receptors that ‘glucocorticoids’ such as cortisol normally attach to. By blocking these receptors, mifepristone prevents cortisol from working and reduces the symptoms of high cortisol levels.

What is the stage of development of this medicine?

The effects of mifepristone have been evaluated in experimental models.

At the time of submission of the application for orphan designation, no clinical trials in patients with endogenous hypercortisolism had been started.

At the time of submission, mifepristone was not authorised anywhere in the world for endogenous hypercortisolism. Orphan designation of mifepristone had been granted in the United States of America for the condition.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 7 January 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>Mifepristone</p>
Active substanceMifepristone
Medicine Name
Disease/conditionTreatment of hypercortisolism (Cushing’s syndrome) of endogenous origin
Date of decision26/02/2009
Orphan decision numberEU/3/09/614

Review of designation

Sponsor’s contact details:

216, boulevard Saint-Germain
75007 Paris
Telephone: +33 1 53 57 37 47
Telefax: +33 1 53 57 37 40

Patients’ associations contact points:

Ligue Nationale Contre le Cancer
14 Rue Corvisart
75013 Paris
Telephone: +33 1 53 55 24 00
Telefax: +33 1 43 36 91 10

National Alliance of Childhood Cancer Patient Organisations
PO Box 176
Bromley BR2 7YN
United Kingdom
Telephone: +44 121 624 4734

Deutsche Krebshilfe e.V.
Buschstr. 32
53113 Bonn
Telephone: +49 2 287 29 900
Telefax: +49 2 287 29 90 11