EU/3/09/671

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Orphan designation

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.

For a list of the administrative updates to this public summary of opinion please refer to the PDF document below.

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).


*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.

Key facts

Product details for <p>Pasireotide</p>
Active substancePasireotide
Medicine NameSignifor
Disease/conditionTreatment of Cushing’s disease
Date of decision08/10/2009
OutcomePositive
Orphan decision numberEU/3/09/671

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*.


*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.

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

The Committee for Medicinal Products for Human Use (CHMP) recommended the authorisation of Signifor for the treatment of adult patients with Cushing’s disease for whom surgery is not an option or for whom surgery has failed.

This falls within the scope of the product’s designated orphan indication, which is treatment of Cushing’s disease.

The COMP concluded that there had been no change in the seriousness of the condition since the orphan designation in 2009. Cushing’s disease remains a condition that is debilitating in the long term and life-threatening, particularly due to its complications resulting from the high levels of cortisol, which include cardiovascular disease, diabetes, clotting disorders, muscular weakness, osteoporosis and psychiatric conditions.

Prevalence of the condition

The sponsor provided recent scientific literature on the prevalence of Cushing’s disease. On the basis of this information and the knowledge of the COMP, the COMP concluded that the prevalence of Cushing’s disease 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 still estimated to be approximately 0.46 people in 10,000. This is equivalent to a total of around 23,000 people in the EU.

Existence of other satisfactory methods of treatment

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

Significant benefit over existing treatments

The COMP concluded that the claim of a significant benefit of Signifor over surgical treatment is justified on the basis of a clinically relevant advantage in the sub-group of patients with Cushing’s disease for whom surgery has failed or is not an option.

When comparing Signifor with other medicines used in Cushing’s disease, the COMP noted that Signifor has a different mechanism of action that directly targets the cause of the disease (i.e. the overproduction of adrenocorticotropic hormone (ACTH) by the pituitary gland). This results in a reduction of the risk of developing secondary pituitary tumours, which justifies the claim of significant benefit over currently authorised medicines.

Therefore, although other satisfactory methods for the treatment of this condition have been authorised in the EU, the COMP concluded that Signifor is of significant benefit for patients affected by Cushing’s disease.

Conclusions

Based on the data submitted and the scientific discussion within the COMP, the COMP considered that Signifor still meets the criteria for designation as an orphan medicinal product and that it should remain in the Community register of orphan medicinal products.

Related information

Sponsor’s contact details:

Novartis Europharm Limited
Wimblehurst Road
Horsham
West Sussex
RH12 5AB
United Kingdom
Tel. +44 (0)1403 272827
Fax +44 (0)1403 323060
E-mail: pio_donizete.zapella@novartis.com

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.