EU/3/06/411: 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.

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 population at risk of developing graft versus host disease was approximately 0.2 in 10,000 people in the European Union (EU)*. This is equivalent to a total of around 10,000 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 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. This represents a population of 459,700,000 (Eurostat 2004).

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 recombinant fusion protein consisting of the extracellular portion of CD95 fused to the Fc part of a human IgG1 molecule might be of potential significant benefit for the prevention of graft versus host disease, 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.

Antibodies are proteins of the immune system that can bind to specific structures and help the body fight infections and other diseases. IgG1 is one type of antibody and CD95 is a protein that is located on some cells of the immune system. This medicinal product is an artificially engineered antibody-like compound where parts of CD95 and IgG1 proteins have been coupled together (fusion protein). It is thought to act by blocking the immune cells from attacking healthy tissues of the patient, thus preventing graft versus host disease.

The effects of recombinant fusion protein consisting of the extracellular portion of CD95 fused to the Fc part of a human IgG1 molecule were evaluated in experimental models.

At the time of submission of the application for orphan designation, no clinical trials in patients at risk of graft versus host disease were initiated.

Recombinant fusion protein consisting of the extracellular portion of CD95 fused to the Fc part of a human IgG1 molecule was not authorised anywhere worldwide for the prevention of graft versus host disease, nor designated as orphan medicinal product elsewhere for this condition, at the time of submission.

According to Regulation (EC) No 141/2000 of 16 December 1999, the Committee for Orphan Medicinal Products (COMP) adopted on 6 September 2006 a positive opinion recommending the grant of the above-mentioned 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 Community) 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.