EU/3/16/1799: 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 'localised' if only one site of the body is affected, or 'diffuse' when several sites are affected. It usually affects the hand joints 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 less than 3 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 154,000 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 513,700,000 (Eurostat 2016).

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 and medicines to reduce inflammation.

Patients with tenosynovial giant cell tumours produce too much of a protein called colony-stimulating factor 1 (CSF1). This causes a build-up of immune cells called macrophages in joints, leading to the outgrowths.

Cabiralizumab attaches to and blocks the receptor to which CSF1 usually attaches, called CSF1R. This prevents CSF1 from working and is therefore expected to prevent outgrowths in the joints and thus delay the onset of symptoms of the disease.

The effects of cabiralizumab have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with cabiralizumab in patients with tenosynovial giant cell tumour, localised and diffuse type were ongoing.

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

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 4 November 2016 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.