EU/3/10/808: Orphan designation for the treatment of graft-versus-host disease

Graft-versus-host disease (GvHD) is a complication that can affect patients who have received allogeneic haematopoietic (blood) stem-cell transplantation (HCT). This is a complex procedure used to treat diseases such as leukaemia or multiple myeloma (cancers of the white blood cells), whereby a patient receives stem cells from a matched donor to help restore the bone marrow, which produces new blood cells.

In GvHD, the transplanted cells recognise the patient as 'foreign' and attack the patients' organs, such as the stomach, gut, skin and liver, leading to organ damage. GvHD may happen shortly after transplantation or later on, in which case a wider range of organs can be involved. GvHD is a serious and life-threatening disease with a high mortality rate.

At the time of designation, GvHD affected less than 0.4 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 20,000 people*, and is below the threshold 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 27), Norway, Iceland and Liechtenstein. At the time of designation, this represented a population of 506,300,000 (Eurostat 2010).

At the time of submission of the application for orphan drug designation, several medicines were authorised in the European Union (EU) for GvHD, such as ciclosporin and corticosteroids. Treatment aimed to reduce the activity of immune cells involved in GvHD, thereby reducing their ability to attack the patient's organs.

The sponsor has provided sufficient information to show that murine monoclonal antibody against CD26 might be of significant benefit for patients with GvHD because early studies indicate that it might improve the treatment particularly of patients who do not respond to corticosteroids. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

This medicine is a monoclonal antibody (a type of protein) that has been designed to attach to a receptor called CD26, which is present on the surface of T-cells. These are cells of the immune system that are involved in GvHD.

CD26 is responsible for stimulating the T-cells to divide. By attaching to CD26, this medicine is expected to block its activity, reducing the rate at which the T-cells multiply. This reduces the number of activated T-cells and lowers the risk of these cells attacking the patient's organs.

The effects of murine monoclonal antibody against CD26 have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with the medicine in patients with GvHD were planned.

At the time of submission, murine monoclonal antibody against CD26 was not authorised anywhere in the EU for GvHD or designated as an orphan medicinal product elsewhere for this condition.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 9 September 2010 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.