EU/3/07/447: Orphan designation for the treatment of gastrointestinal stromal tumours

Gastrointestinal stromal tumours (GISTs) belong to a special group of gastro-intestinal tumours, called sarcomas. Sarcomas may occur also in other soft tissues of the body. They are cancers of the tissues that support, surround and protect the organs. The cause of GISTs is largely unknown. GISTs are most common in the stomach (60-70%), followed by the small intestine (20-30%), and then the colon and rectum (5%). GISTs occur predominantly in middle-aged and older people, and are considered as a life-threatening condition.

At the time of designation, GISTs affected approximately 2 in 10,000 people in the European Union (EU). This was equivalent to a total of around 100,000 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 500,300,000 (Eurostat 2007).

The current methods of treatment of GISTs are surgical removal of the tumour, and treatment with one (authorised) medicinal product, that belongs to a group of substances called tyrosine-kinase inhibitors. These products are aimed at slowing down and potentially stopping tumour growth.

Nilotinib hydrochloride monohydrate might be of potential significant benefit for the treatment of malignant GISTs, mainly because it could act in a different way to currently authorised product, and might thus improve the long-term outcome of the patients. This assumption will have to be confirmed at the time of marketing authorisation. This will be necessary to maintain the orphan status.

Enzymes are proteins produced by the human body that speed up the transformation of certain substances into other substances. Nilotinib blocks (inhibits) a certain class of enzymes called tyrosine kinases. These enzymes play role in a cascade of molecular reactions that bring a certain signal from outside the cell into the cell thereby controlling the growth of cells. In chronic myeloid leukaemia, the function of these enzymes is disturbed causing uncontrolled growth and multiplication of the cancer cells. Nilotinib might, by inhibition of one or more of these enzymes activity help slowing down or stopping the further growth of the cancer cells.

The effects of nilotinib gastrointestinal stromal tumours have been evaluated in experimental models.

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

Nilotinib hydrochloride monohydrate was not authorised anywhere worldwide for chronic myeloid leukaemia or designated as orphan medicinal product elsewhere for this condition, at the time of submission.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 8 March 2007 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.