EU/3/13/1171: Orphan designation for the prevention of rejection following solid organ transplantation

Graft rejection following solid organ transplantation is a problem that can occur when the body rejects a transplanted organ. Graft rejection is caused by the patient's immune system (the body's natural defences) recognising the transplanted graft as 'foreign'. This results in inflammation and damage to the organs.

Graft rejection following solid organ transplantation is a life-threatening and debilitating condition because the transplanted organ may function poorly or fail.

At the time of designation, the number of patients at risk of organ graft rejection was estimated to be not more than 0.9 people in 10,000 in the European Union (EU). This was equivalent to a total of not more than 46,000 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 512,200,000 (Eurostat 2013).

At the time of designation, several medicines to suppress the immune system in order to prevent rejection after transplantation were authorised in the EU. These included the antibodies basiliximab and rabbit anti-human thymocyte immunoglobulin. In addition immunosuppressive medicines such as ciclosporin, tacrolimus, mycophenolates and corticosteroids were used as long-term treatment to prevent rejection.

The sponsor has provided sufficient information to show that this medicine might be of significant benefit to patients at risk of graft rejection based on laboratory studies suggesting that when used together with standard immunosuppressive treatment it may prolong the survival of transplanted organs compared with immunosuppressive treatment alone. This assumption will have to be confirmed at the time of marketing authorisation in order to maintain the orphan status.

The medicine is made using a type of the patient's own blood cells called regulatory T cells. Regulatory T cells are white blood cells that moderate the actions of other white blood cells, thereby maintaining the normal activity of the immune system, preventing excessive immune activity that would otherwise lead to immune diseases or severe reactions. In patients undergoing transplantation, this medicine is expected to moderate the activity of the other white blood cells against the transplanted organ, thereby reducing the risk that the organ will fail.

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, no clinical trials with the medicine for preventing graft rejection following solid organ transplantation had been started.

At the time of submission, the medicinal product was not authorised anywhere in the EU for this use or designated as an orphan medicinal product elsewhere.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 4 September 2013 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.