EU/3/18/2063: Orphan designation for the treatment in solid organ transplantation

Solid organ transplantation is a surgical procedure in which a diseased organ, such as the heart, lungs, liver or kidney, is replaced with an organ from a donor.

Transplantation is a very complex procedure. During transplantation, the organ to be transplanted can become damaged because of the interruption and restoration of blood supply to the organ. In addition, graft rejection can occur after transplantation, 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.

These complications can be debilitating and life-threatening because they may result in the transplanted organ not working properly.

At the time of designation, approximately 0.7 in 10,000 people in the European Union (EU) were undergoing solid organ transplantation every year. This was equivalent to a total of 36,000 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).

At the time of designation, several medicines were authorised in the EU to prevent or treat graft rejection in solid organ transplantation. These include antibodies such as antilymphocyte immunoglobulin and thymoglobulin and other medicines that suppress immune processes such as azathioprine, basilixmab, ciclosporin, mycophenolate mofetil, tacrolimus, 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 undergoing solid organ transplantation. Early studies indicate that the medicine could help the recipient’s body accept the transplant, allowing the patient to reduce use of medicines that suppress the immune system.

This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

To make the medicine, stem cells (cells that can develop into different types of blood cells) and T cells (cells of the immune system) are collected from the organ donor. These cells are processed and then given to the patient who has received the transplant, where they are expected to grow and multiply. This results in the patient’s immune system containing a mixture of their own immune cells and the donor’s immune cells. This is expected to prevent the immune system recognising the transplanted donor organ as ‘foreign’ and attacking it, and increase the chances that the transplant is successful.

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 undergoing solid organ transplantation were ongoing.

At the time of submission, the medicine was not authorised anywhere in the EU for 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 19 July 2018 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.