EU/3/14/1421: Orphan designation for the treatment of gastrointestinal stromal tumours

Gastrointestinal stromal tumours (GIST) belong to 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. 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 persons, and are considered a life-threatening condition because the tumours could come back and also spread to other organs.

At the time of designation, GIST affected approximately 2.2 in 10,000 people in the European Union (EU). This was equivalent to a total of around 112,000 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 511,100,000 (Eurostat 2014).

At the time of designation, treatment of GIST mainly consisted in surgical removal of 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 ponatinib hydrochloride might be of significant benefit for patients with GIST because data from early studies showed that the medicine may improve the outcome of patients whose tumour had progressed after treatment with available medicines. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

Ponatinib hydrochloride belongs to a group of medicines called 'tyrosine kinase inhibitors', which act by blocking enzymes known as tyrosine kinases.

The medicine is expected to work in GIST by blocking the activity of a tyrosine kinase called 'KIT', which is often abnormal (mutated) and overactive in GIST cells, causing them to multiply uncontrollably. By blocking KIT, as well as other kinases such as PDGF, the medicine is expected to help to slow down or stop the growth of the tumour.

In the EU, ponatinib is already authorised as Iclusig for the treatment of leukaemia (a cancer of the blood).

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, ponatinib hydrochloride was not authorised anywhere in the EU for GIST 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 11 December 2014 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.