EU/3/15/1457: Orphan designation for the treatment of tenosynovial giant cell tumour, localised and diffuse type

Tenosynovial giant cell tumour is a condition where the tissue surrounding the joints and tendons, called the synovial lining or synovium, expands abnormally forming outgrowths of the joint. It is known as 'diffuse' if the entire synovium is affected, or 'localised' if only a section of the synovium is affected. It usually affects the hand joint of young adults and is characterised by pain, swelling and stiffness of the joint.

Tenosynovial giant cell tumour is a long-term debilitating disease because it causes the destruction of joints.

At the time of designation, tenosynovial giant cell tumour, localised and diffuse type, affected not more than 2 in 10,000 people in the European Union (EU). This was equivalent to a total of not more than 153,000 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 512,900,000 (Eurostat 2015).

At the time of designation, no satisfactory methods were authorised in the EU for the treatment of tenosynovial giant cell tumour and treatment consisted of surgery.

The medicine is expected to work by blocking a receptor called CSF1R to which a protein called macrophage colony-stimulating factor (M-CSF) attaches. M-CSF is produced in large amounts by tenosynovial giant cell tumours, where it stimulates immune cells called macrophages to accumulate in the joints and cause the outgrowths. By attaching and blocking CSF1R, the medicine is expected to block the activity of M-CSF, preventing tumour growth and helping to delay the onset of the symptoms of the disease.

The effects of the medicine have been evaluated in experimental models.

At the time of submission of the application for orphan designation, a clinical trial with the medicine in patients with tenosynovial giant cell tumour, localised and diffuse type was ongoing.

At the time of submission, the medicine was not authorised anywhere in the EU for tenosynovial giant cell tumour, localised and diffuse type. Orphan designation of the medicine had been granted in United States for treatment of pigmented villonodular synovitis/giant cell tumour of the tendon sheath.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 12 February 2015 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.