EU/3/09/671: Orphan designation for the treatment of Cushing's disease

Cushing's disease is a disease characterised by an excess of the hormone cortisol in the blood. It is caused by a tumour of the pituitary gland (a gland located at the base of the brain) that produces large amounts of adrenocorticotropic hormone (ACTH), which in turn stimulates the production of excess cortisol. Patients with Cushing's disease have 'central' weight gain (affecting the face and torso but not the limbs), growth of fat above the collar bone and the back of the neck, a roundish face, easy bruising, excessive growth of coarse hair on the face, weakening of the muscles and bones, depression and high blood pressure.

Cushing's disease 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.

At the time of designation, Cushing's disease affected approximately 0.4 in 10,000 people in the European Union (EU). This was equivalent to a total of around 20,000 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. At the time of designation, this represented a population of 504,800,000 (Eurostat 2009).

At the time of designation, the main treatment for Cushing's disease involved surgery to remove the tumour responsible for causing the high cortisol levels, sometimes followed by radiotherapy (treatment with radiation). Several medicines were used in the EU to reduce the production of cortisol or prevent it from working.

The sponsor has provided sufficient information to show that pasireotide might be of significant benefit for patients with Cushing's disease because it might improve the treatment of patients with this condition and may represent an alternative to surgery when surgery is not an option or has failed. These assumptions will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

Pasireotide is a 'somatostatin analogue', a copy of the natural hormone somatostatin. Like somatostatin, pasireotide is expected to attach to somatostatin receptors. These receptors are found in high amount in tumour cells, including tumours of the pituitary gland. By attaching to somatostatin receptors, pasireotide is expected to block the release of ACTH. This may result in the reduction of cortisol levels, helping to relieve the symptoms of Cushing's disease.

The effects of pasireotide have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials in patients with Cushing's disease were ongoing.

At the time of submission, pasireotide was not authorised anywhere in the EU for Cushing's disease or designated as 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.

Update: Pasireotide (Signifor) was authorised in the EU on 24 April 2012 for treatment of adult patients with Cushing's disease for whom surgery is not an option or for whom surgery has failed.

• 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.