EU/3/09/671 - orphan designation for treatment of Cushing's disease

pasireotide

Overview

On 8 October 2009, orphan designation (EU/3/09/671) was granted by the European Commission to Novartis Europharm Limited, United Kingdom, for pasireotide for the treatment of Cushing's disease.

Pasireotide in treatment of Cushing's disease has been authorised in the EU as Signifor since 24 April 2012.

The sponsorship was transferred to Novartis Europharm Limited, Ireland, in May 2018.

The sponsorship was transferred to Recordati Rare Diseases, France in May 2020.

Please note that this product was withdrawn from the Community Register of designated orphan medicinal products in April 2022 at the end of the 10-year period of market exclusivity.

What is 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.

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

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).

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*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).

What treatments are available?

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.

How is this medicine expected to work?

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.

What is the stage of development of this medicine?

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.

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.

EU/3/09/671: Public summary of positive opinion for orphan designation of pasireotide for the treatment of Cushing’s disease

AdoptedReference Number: EMEA/COMP/455317/2009 Rev. 2

Key facts

• Active substance:
  pasireotide
• Medicine name:
  Signifor
• Intended use:
  Treatment of Cushing's disease
• Orphan designation status:
  Expired
• EU designation number:
  EU/3/09/671
• Date of designation:
  08/10/2009
• Sponsor:

  Recordati Rare Diseases ;

Review of designation

During its meeting of 7-8 February 2012, the Committee for Orphan Medicinal Products (COMP) reviewed the designation EU/3/09/671 for Signifor (pasireotide) as an orphan medicinal product for the treatment of Cushing's disease. 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. As other satisfactory methods of treatment for patients with this condition are authorised in the European Union (EU), the COMP also looked at the significant benefit of the product over existing treatments. The COMP recommended that the orphan designation of the medicine be maintained*.

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*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 EU. This means that in the 10 years after its authorisation, similar products with a comparable therapeutic indication cannot be placed on the market.