EU/3/05/305: Orphan designation for the treatment of dermatofibrosarcoma protuberans

Dermatofibrosarcoma is a relatively slowly growing skin cancer, which can occur anywhere in the body but most of them occur on the trunk or on the arms and legs. The pattern of growth is usually slow and persistent, and as the lesion enlarges over many years, it becomes a knob (protuberant). The cancer consists of one or several hard small lumps that are usually covered by a dark red-blue skin, which tends to be fixed to the lumps. As it grows slowly it is often ignored until it grows large. This type of skin cancer has the potential to infiltrate in the local surrounding tissue but will only rarely spread to other parts of the body. Because of its local aggressive nature, surgical excision is often extensive and can include underlying tissues such as muscles and bone. This may lead to severe restrictions of the use of that part of the body. Despite extensive surgery, the cancer often comes back. Dermatofibrosarcoma protuberans is chronically debilitating and in some cases can be life threatening due to extensive invasion.

At the time of designation, dermatofibrosarcoma protuberans affected less than 1 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 47,000 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 25), Norway, Iceland and Liechtenstein. At the time of designation, this represented a population of 466,600,000 (Eurostat 2005).

No medicinal products were authorised for the treatment of dermatofibrosarcoma protuberans in the Community at the time of submission of the application for orphan drug designation. The treatment option is limited to various surgical procedures.

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 to bring a certain signal from outside the cell into the cell thereby controlling the growth of the cells. 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.

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

Imatinib mesilate was not marketed anywhere worldwide for dermatofibrosarcoma protuberans, at the time of submission. Orphan designation of imatinib mesilate was granted in Europe and in the United States for chronic myeloproliferative leukaemia and for gastrointestinal stromal tumours.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 13 July 2005 recommending the granting of this designation.

Update: Imatinib mesilate (Glivec) has been authorised in the EU since 13 September 2006 for the treatment of adult patients with unresectable dermafibrosarcoma protuberans (DFSP) and adult patients with recurrent and/or metastatic DFSP who are not eligible for surgery.

• 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