EU/3/01/061: Orphan designation for the treatment of malignant gastrointestinal stromal tumours

Malignant gastrointestinal stromal tumours are the most common subtype of gastro-intestinal sarcomas, which belong to the group of soft tissue sarcomas. Soft tissue sarcomas are cancers of the tissues that support, surround and protect the organs of the body, such as muscle tissue and fat tissue. The cause of gastrointestinal stromal tumours is largely unknown. Gastrointestinal stromal tumours are most common in the stomach (60-70%), followed by small intestine (20-30%), and colon and rectum (5%). Gastrointestinal stromal tumours occur predominantly in middle-aged and older persons and are considered as a life-threatening condition.

At the time of designation, malignant gastrointestinal stromal tumours affected approximately 0.06 in 10,000 people in the European Union (EU). This was equivalent to a total of around 2,300 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. At the time of designation, this represented a population of 378,800,000 (Eurostat 2001).

At the time of submission of the application for orphan drug designation the method of treatment was surgery. There were no medicinal products authorised for the condition in the Community at the time of submission.

Enzymes are proteins produced by the human body that speed up the conversion of certain substances into other substances. Imatinib mesilate blocks (inhibits) the enzyme tyrosine kinase. This enzyme plays a role in a cascade of molecular reactions responsible of bringing a certain external signal inside the cell, thereby controlling the growth of the cell itself. In cancer cells, the function of this enzyme is disturbed causing uncontrolled growth and multiplication of the cancer cells. Imatinib mesilate might, by inhibition of this enzyme activity, help in slowing down or stopping the further growth of the cancer cells.

The effects of imatinib mesilate were evaluated in experimental models.

At the time of submission of the application for orphan designation, one clinical trial in patients with malignant gastrointestinal stromal tumours was ongoing.

Imatinib mesilate was not marketed anywhere worldwide for the treatment of malignant gastrointestinal stromal tumours 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 7 September 2001 recommending the granting of this designation.

Update: Imatinib mesilate (Glivec) was authorised in the EU on 24 May 2002 for the treatment of adult patients with Kit (CD 117) positive unresectable and/or metastatic malignant gastrointestinal stromal tumours (GIST).

• 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