EU/3/13/1113: Orphan designation for the prevention of graft rejection following solid organ transplantation

Graft rejection following solid-organ transplantation is a problem that can occur when the recipient's body rejects the 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 condition because the transplanted organ may fail and because medication is required to supress the patient's immune system, which can result in infections and malignancies.

At the time of designation, the number of patients at risk of organ graft rejection following solid organ transplantation was estimated to be not more than 0.9 people in 10,000 per year in the European Union (EU). This was equivalent to a total of not more than 46,000 people per year*, and is below the ceiling for orphan designation. 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. At the time of designation, this represented 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 include the antibodies basiliximab and rabbit anti-human thymocyte immunoglobulin, which were used at time of transplantation.

The sponsor has provided sufficient information to show that this medicine might be of significant benefit to patients at risk of graft rejection because early studies suggest it may be more effective than existing treatments. This assumption will have 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 recognise and attach to a receptor called 'alpha beta T-cell receptor', which is present on the surface of cells of the immune system called alpha beta T-cells which are involved in the immune response following solid organ transplantation. Alpha beta T-cell receptor is responsible for identifying certain structures (antigens) produced by the transplanted organ as 'foreign', which initiates the immune response. By attaching to the alpha beta T-cell receptor, this medicine is expected to block its activity, making alpha beta T-cells unable to recognise the antigens. This is expected to reduce the immune reaction to the transplanted organ.

The effects of murine IgM monoclonal antibody binding to alpha beta T-cell receptor have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with the medicine in patients who received a solid-organ transplant were ongoing.

At the time of submission, this medicine was not authorised anywhere in the EU for the prevention of graft rejection following solid-organ transplantation. Orphan designation of the medicine had been granted in the United States for the prevention of this condition.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 6 February 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.