EU/3/12/977 - orphan designation for treatment of adrenal cortical carcinoma
Linsitinib
OrphanHuman
Overview
Please note that this product was withdrawn from the Community register of designated orphan medicinal products in February 2013 on request of the sponsor.
On 2 April 2012, orphan designation (EU/3/12/977) was granted by the European Commission to Astellas Pharma Europe B.V., the Netherlands, for linsitinib for the treatment of adrenal cortical carcinoma.
Adrenal cortical carcinoma is a cancer of the adrenal cortex, which is the outside layer of the adrenal glands, small glands located above the kidneys. The adrenal cortex produces several steroid hormones, including sex hormones (which cause the body to have masculine or feminine characteristics), aldosterone (which helps to regulate the body's blood pressure) and cortisol (also known as the stress hormone because it is released in response to stress). In adrenal cortical carcinoma, too much of one or more of these steroid hormones are produced. Symptoms associated with adrenal cortical carcinoma may include weakening of the muscles and bones, high blood pressure and the development of abnormal masculine or feminine features if the sex hormones are affected.
Adrenal cortical carcinoma is a long-term debilitating and life-threatening disease due to poor overall survival which ranges between one and two years in the advanced stages of the disease.
At the time of designation, adrenal cortical carcinoma affected approximately 0.05 in 10,000 people in the European Union (EU). This was equivalent to a total of 2,500 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 509,000,000 (Eurostat 2012).
At the time of designation, mitotane was authorised in the EU to treat the symptoms of adrenal cortical carcinoma, when the cancer is unrespectable (cannot be removed by surgery), is metastatic (has spread to other parts of the body) or has relapsed (returned after treatment). For small tumours, surgery was used to remove the cancer cells.
The sponsor has provided sufficient information to show that linsitinib might be of significant benefit for patients with adrenal cortical carcinoma because it works in a different way to existing treatments and early studies show that it may improve the outcome of patients whose disease is advanced for whom no other effective therapy exists. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.
Linsitinib is a 'protein tyrosine-kinase inhibitor', which means that it works by blocking enzymes known as tyrosine kinases. These enzymes can be found in some receptors on the surface of cancer cells, including the insulin-like-growth-factor-1 receptor (IGF-1R), which is a receptor for a protein called insulin-like growth factor (IGF). IGF-1R is involved in stimulating the cells to divide uncontrollably. By blocking these receptors, linsitinib is expected to stop cell division and lead to cell death. This is expected to slow down the growth or cause the shrinkage of adrenal cortical carcinoma tumours.
The effects of linsitinib have been evaluated in experimental models.
At the time of submission of the application for orphan designation, clinical trials with linsitinib in patients with adrenal cortical carcinoma were ongoing.
At the time of submission, linsitinib was not authorised anywhere in the EU for adrenal cortical carcinoma or designated as an 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 February 2012 recommending the granting of this designation.
- 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 EU) 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
- Active substance
- Linsitinib
- Intended use
- Treatment of adrenal cortical carcinoma
- Orphan designation status
- Withdrawn
- EU designation number
- EU/3/12/977
- Date of designation
- Sponsor
Astellas Pharma Europe B.V
Review of designation
Please note that this product was withdrawn from the Community register of designated orphan medicinal products in February 2013 on request of the sponsor, before a marketing authorisation had been granted.
EMA list of opinions on orphan medicinal product designation
EMA publishes information on orphan medicinal product designation adopted by the Committee for Orphan Medicinal Products (COMP) on the IRIS online platform:
Patients' organisations
For contact details of patients’ organisations whose activities are targeted at rare diseases, see:
European Organisation for Rare Diseases (EURORDIS), a non-governmental alliance of patient organisations and individuals active in the field of rare diseases.
Orphanet, a database containing information on rare diseases, which includes a directory of patients’ organisations registered in Europe.
EU register of orphan medicines
The list of medicines that have received an orphan designation in the EU is available on the European Commission's website: