Signifor

pasireotide

This is a summary of the European public assessment report (EPAR) for Signifor. It explains how the Committee for Medicinal Products for Human Use (CHMP) assessed the medicine to reach its opinion in favour of granting a marketing authorisation and its recommendations on the conditions of use for Signifor.

What is Signifor?

Signifor is a medicine that contains the active substance pasireotide. It is available as a solution for injection.

What is Signifor used for?

Signifor is used to treat adults with Cushing’s disease when surgery has failed or is not an option.

Cushing’s disease is caused by a tumour of the pituitary gland (a gland located at the base of the brain) releasing too much of a hormone called ACTH that stimulates the production of too much cortisol (a hormone also known as the ‘stress hormone’ because it is released in response to stress).

Because the number of patients with Cushing’s disease is low, the disease is considered ‘rare’, and Signifor was designated an ‘orphan medicine’ (a medicine used in rare diseases) on 8 October 2009.

The medicine can only be obtained with a prescription.

How is Signifor used?

Signifor is given as an injection under the skin at an initial dose of 0.6 mg twice a day in different injection sites (preferably at the top of the thigh and the abdomen). Patients should be trained on how to inject themselves. After two months, the patient’s response to treatment should be evaluated. If a significant reduction in blood cortisol levels is seen, treatment should be continued for as long as the patient benefits from it. The dose may need to be increased to 0.9 mg in some patients, while the doctor will need to consider stopping Signifor in patients who have not responded after two months. If side effects develop the dose may need to be temporarily reduced.

In patients with moderate liver problems, the starting dose should be reduced to 0.3 mg twice a day and the maximum recommended dose is 0.6 mg twice a day.

How does Signifor work?

Pasireotide is a ‘somatostatin analogue’, a copy of the natural hormone somatostatin, which is known to block the release of ACTH. Receptors for somatostatin are usually found in high amounts on tumour cells, including tumours of the pituitary gland which cause Cushing’s disease. Like somatostatin, pasireotide attaches to these receptors and blocks the release of excessive ACTH. Since ACTH stimulates production of cortisol, reducing ACTH helps to reduce cortisol levels in the body, thereby relieving the symptoms of the disease.

How has Signifor been studied?

The effects of Signifor were first tested in experimental models before being studied in humans.

Signifor was studied in 165 adult patients with Cushing’s disease where surgery was not appropriate. Patients were treated with Signifor at either 0.6 mg twice a day or 0.9 mg twice a day. The main measure of effectiveness was the proportion of patients whose cortisol level in the urine normalised after six months.

In addition, the study also looked at the proportion of patients who partially responded to treatment and whose cortisol level in the urine decreased by at least 50% after six months.

What benefit has Signifor shown during the studies?

Signifor was shown to be effective in reducing cortisol levels. The study showed that 15% of patients receiving 0.6 mg Signifor (12 patients out of 82) and 26% of patients receiving 0.9 mg Signifor (21 patients out of 80) had normal urine cortisol levels within six months.

In 34% of patients receiving 0.6 mg Signifor and 41% of patients receiving 0.9 mg Signifor urine cortisol levels decreased by at least 50% within six months.

What is the risk associated with Signifor?

The most common side effects with Signifor (seen in more than 1 patient in 10) are hyperglycaemia (high blood sugar levels), diabetes, diarrhoea, abdominal pain (stomach ache), nausea (feeling sick), cholelithiasis (gallstones), injection site reactions, fatigue (tiredness) and increased blood levels of glycosylated haemoglobin (a substance which gives an indication of how well the blood glucose is controlled). For the full list of all side effects reported with Signifor, see the package leaflet.

Signifor must not be used in patients who are hypersensitive (allergic) to the active substance or any of the other ingredients. It must not be used in patients with severe liver problems.

Why has Signifor been approved?

The Committee took the view that, although the proportion of patients who responded and whose cortisol levels in the urine normalised was small, Signifor could be of benefit in patients who have failed surgery or where surgery is not an option. It also considered that a partial response may be of benefit in these patients. After two months of treatment with Signifor, it is possible to identify which patients are responding and to stop treatment in those who are not responding.

Regarding the safety of Signifor, the identified side effects were considered to be manageable and similar to other medicines of its class. The CHMP therefore concluded that the benefits of Signifor outweigh its risks and recommended that it be granted marketing authorisation.

Other information about Signifor

The European Commission granted a marketing authorisation valid throughout the European Union for Signifor on 24 April 2012.

For more information about treatment with Signifor, read the package leaflet (also part of the EPAR) or contact your doctor or pharmacist.

This EPAR was last updated on 21/05/2013 .

More detail is available in the summary of product characteristics

Product details

Publication details

Product information

21/03/2013  Signifor -EMEA/H/C/002052 -II/0005

Contents

• Annex I - Summary of product characteristics
• Annex IIA - Manufacturing-authorisation holder responsible for batch release
• Annex IIB - Conditions of the marketing authorisation
• Annex IIIA - Labelling
• Annex IIIB - Package leaflet

Please note that the size of the above document can exceed 50 pages.

You are therefore advised to be selective about which sections or pages you wish to print.

Pharmacotherapeutic group

Pituitary and hypothalamic hormones and analogues

Therapeutic indication

Signifor is indicated for the treatment of adult patients with Cushing’s disease for whom surgery is not an option or for whom surgery has failed.

Changes since initial authorisation of medicine

Initial marketing-authorisation documents