EU/3/08/561: Orphan designation for the prevention of graft-versus-host disease

Graft-versus-host disease (GvHD) is a complication of bone marrow transplant. The bone marrow is the spongy tissue inside the large bones in the body that makes blood cells and platelets (components that help the blood to clot). Bone marrow transplants are used for diseases such as leukaemia or multiple myeloma (cancer of the white blood cells).

In GvHD, the cells in the transplanted bone marrow react against the patients' organs, such as the stomach, gut, skin and liver, leading to organ damage. GvHD may happen in the short term, or later after transplantation, in which case a wider range of organs can be involved. GvHD is a serious, life-threatening disease.

At the time of designation, the number of patients at risk of GvHD was estimated to be approximately 0.2 people in 10,000 in the European Union (EU). This was equivalent to a total of around 10,000 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 27), Norway, Iceland and Liechtenstein. At the time of designation, this represented a population of 502,800,000 (Eurostat 2008).

Several products were authorised for the condition in some countries in the Community at the time of submission of the application for orphan drug designation.
Current methods for preventing GvHD aim to reduce the activity of the immune system (the body's natural defences). These methods work by targeting cells that divide often, such as the immune system cells.

Satisfactory argumentation has been submitted by the sponsor to justify the assumption that donor lymphocyte preparation depleted of functional alloreactive T-cells might be of potential significant benefit for the prevention of GvHD, mainly because it has a new mechanism of action. This assumption will have to be confirmed at the time of marketing authorisation. This will be necessary to maintain the orphan status.

The product is a preparation of a type of immune system cell called T-cells. It involves the use of a chemical compound that reacts to light, and destroys the T-cells in the cell preparation called donor lymphocyte preparation that could attack the patient's organs.

This cell preparation is given to patients whose immune system is weak after chemotherapy. It is thought to enable the immune system to be rebuilt with healthy T-cells.

The effects of donor lymphocyte preparation depleted of functional alloreactive T-cells have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials in patients who have undergone a bone marrow transplant were ongoing.

Donor lymphocyte preparation depleted of functional alloreactive T-cells was not authorised anywhere worldwide for prevention of GvHD at the time of submission. Orphan designation of donor lymphocyte preparation depleted of functional alloreactive T-cells had been granted in the United States of America for immune reconstitution and prevention of GvHD following allogeneic haematopoietic stem cell transplantation.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 11 June 2008 recommending the granting of this designation.

• the seriousness of the condition;
• the existence of alternative methods of diagnosis, prevention or treatment;
• and either the rarity of the condition (affecting not more than five in 10,000 people in the Community) or the 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 the quality, safety and efficacy is necessary before a product can be granted a marketing authorisation.