EU/3/14/1426: Orphan designation for the prevention 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. This is a complex procedure used to treat diseases of the blood such as leukaemia (a cancer 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 patient's 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, the number of patients at risk of GvHD was estimated to be approximately 0.4 people in 10,000 in the European Union (EU). This was equivalent to a total of around 20,000 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 511,100,000 (Eurostat 2014).

At the time of designation, several medicines were authorised in the European Union (EU) for the prevention of GvHD, such as cyclosporine and antilymphocyte immunoglobulins (ATG). 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 the medicine might be of significant benefit for patients at risk of GvHD because preliminary studies suggest that the medicine can prevent severe acute GvHD when compared with published data for other treatments. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

This medicine is an advanced medicine that belongs to the group called 'somatic cell therapy products'. These are medicines that contain cells or tissues that have been manipulated to change their biological characteristics so that they can be used to cure, diagnose or prevent a disease.

This medicine contains certain immune cells derived from the blood of the donors who provide the stem-cell transplant. These immune cells are treated in the laboratory to induce and maintain them in an early stage of apoptosis (cell death). These 'dying' cells are then injected into the patients before they are given the stem-cell transplant. The dying cells are expected to help 'shut down' the cells that recognise the patient's cells as 'foreign', thereby preventing the patient's cells from being attacked and reducing the risk of GvHD.

At the time of submission of the application for orphan designation, the evaluation of the effects of the medicine in experimental models was ongoing.

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

At the time of submission, the medicine was not authorised anywhere in the EU for prevention of GvHD. Orphan designation of the medicine had been granted in the United States for this condition.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 11 December 2014 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.