EU/3/17/1936: Orphan designation for the treatment of gastrointestinal stromal tumours

Gastrointestinal stromal tumours (GIST) are a group of cancers of the stomach and bowel called sarcomas, which are characterised by uncontrolled growth of cells in the supporting tissues of these organs. Symptoms include bleeding, anaemia (low red blood cell counts), tiredness, and abdominal (belly) pain and discomfort. GIST are most common in the stomach (60%), followed by the small intestine (30%), and then the colon and rectum (5%). GIST occur predominantly in middle-aged and older people, and are considered life threatening because the tumours could come back and also spread to other organs.

At the time of designation, GIST affected approximately 1.6 in 10,000 people in the European Union (EU). This was equivalent to a total of around 83,000 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 28), Norway, Iceland and Liechtenstein. This represents a population of 515,700,000 (Eurostat 2017).

At the time of designation, GIST were treated mainly by surgery to remove the tumour. The medicines imatinib, sunitinib and regorafenib were authorised in the EU for the treatment of GIST that had spread and could not be surgically removed.

The sponsor has provided sufficient information to show that this medicine might be of significant benefit for patients with GIST because data from early studies showed that it had a beneficial effect in patients whose tumour could not be treated with available medicines or had grown after such treatments. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

In GIST cells, two types of tyrosine kinase enzymes, KIT and PDGFRA, may be abnormal and overactive, which causes GIST cells to multiply out of control. The medicine stops these enzymes from working, including abnormal forms that cannot be blocked by other medicines. Giving the medicine by mouth is expected to stop GIST cells from multiplying and so slow down the growth of the tumours and reduce symptoms of the disease.

The effects of the medicine have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with the medicine in patients with GIST were ongoing.

At the time of submission, the medicine was not authorised anywhere in the EU for GIST. Orphan designation of the medicine had been granted in United States for GIST.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 5 October 2017 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.