EU/3/16/1826: 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 cancer.

At the time of designation, the number of patients at risk of graft rejection following solid organ transplantation was estimated to be approximately 0.6 people in 10,000 in the European Union (EU). This was equivalent to a total of around 31,000 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 at risk of developing 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 513,700,000 (Eurostat 2016).

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 this medicine might be of significant benefit for patients at risk of graft rejection following solid organ transplantation. Early studies showed that giving the medicine before kidney transplantation led to successful transplantation in patients with high levels of antibodies against the donor's organ. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

This medicine is made of an enzyme derived from the bacterium Streptococcus pyogenes, which breaks down antibodies called IgGs. IgGs are produced by the patient receiving the transplant against the transplanted organ. By breaking down IgGs, the medicine is expected to prevent the patient's immune system from attacking the transplanted organ, thereby reducing the risk that the organ will fail.

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 following solid organ transplantation 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. Orphan designation of the medicine had been granted in the United States for this condition.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 8 December 2016 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.