EU/3/07/447

On 13 April 2007, orphan designation (EU/3/07/447) was granted by the European Commission to Novartis Europharm Limited, United Kingdom, for nilotinib hydrochloride monohydrate for the treatment of gastrointestinal stromal tumours.

What are gastrointestinal stromal tumours?

Gastrointestinal stromal tumours (GIST) 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 GIST is largely unknown. GIST 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 persons, and are considered as a life-threatening condition.

What are the methods of treatment available?

The current methods of treatment of GIST 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 GIST, 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.

What is the estimated number of patients affected by the condition*?

Based on the information provided by the sponsor and previous knowledge of the Committee, GIST was considered to affect approximately 2 in 10,000 persons in the European Union, which, at the time of designation, corresponded to about 100,000 persons in the European Union.

*Disclaimer: For the purpose of the designation, the number of patients affected by the condition is estimated and assessed based on data from the European Union (EU 25), Norway, Iceland and Lichtenstein. This represents a population of 459,700,000 (Eurostat 2004). This estimate is based on available information and calculations presented by the sponsor at the time of the application.

How is this medicinal product expected to act?

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.

What is the stage of development of this medicinal product?

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

At the time of submission of the application for orphan designation, clinical trials in patients with gastrointestinal stromal tumours 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.

According to Regulation (EC) No 141/2000 of 16 December 1999, the Committee for Orphan Medicinal Products (COMP) adopted on 8 March 2007 a positive opinion recommending the grant of the above-mentioned designation.

Opinions on orphan medicinal products designations are based on the following cumulative criteria:

• the seriousness of the condition, 
• the existence or not of alternative methods of diagnosis, prevention or treatment and 
• either the rarity of the condition (considered to affect not more than five in ten thousand persons in the Community) or the insufficient return of development investments.

Designated orphan medicinal products are still investigational products which were considered for designation on the basis of potential activity. An orphan designation is not a marketing authorisation. As a consequence, demonstration of the quality, safety and efficacy will be necessary before this product can be granted a marketing authorisation.