EU/3/14/1253: 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' and attacking it. 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 suppress the patient's immune system, which can result in infections and malignancies.

At the time of designation, the number of patients at risk of graft rejection following solid organ transplantation 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 511,100,000 (Eurostat 2014).

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 antithymocyte immunoglobulin, calcineurin inhibitors such as ciclosporin or tacrolimus, azathioprine, mycophenolate mofetil and corticosteroids such as prednisolone or methylprednisolone.

The sponsor has provided sufficient information to show that the medicine might be of significant benefit for patients at risk of graft rejection following solid organ transplantation because early results suggest that combination with existing treatments improves the survival of transplanted organs compared with existing treatments alone and can reduce the need for medicines to suppress the immune system. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

The medicine contains human mesenchymal stromal cells (hMSCs) that have been extracted from donor tissue and grown in a laboratory to increase their numbers. In the body, hMSCs help to regulate the immune system, reducing the activation and growth of cells responsible for attacking foreign bodies and encouraging the growth of other immune cells that can protect the transplanted tissue. By supplying additional hMSCs, the medicine is expected to reduce the immune system's attack on the graft, decreasing inflammation and damage to the graft and lowering the risk of graft rejection, and hence the need for other medicines to suppress the immune system.

The effects of the medicine have been evaluated in experimental models.

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

At the time of submission, the medicine was not authorised anywhere in the EU for prevention of graft rejection following solid organ transplantation or designated as an orphan medicinal product elsewhere for this condition.
In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 6 February 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.