EU/3/10/751: Orphan designation for the prevention of delayed graft function after renal transplantation

Delayed graft function is the failure of a transplanted organ to start working properly in the first few days after the transplant. Delayed graft function can occur following kidney transplants as a result of damage to the organ caused by the interruption and restoration of blood flow. This is called 'ischaemia/reperfusion injury' and is associated with an inflammatory reaction, caused in part by the invasion of neutrophils (a type of white blood cell) into the transplanted organ.

Delayed graft function after renal transplantation is a debilitating and life-threatening condition because of the risk of losing the transplanted kidney.

At the time of designation, the number of patients at risk of delayed graft function after renal transplantation was estimated to be approximately 0.4 people in 10,000 in the European Union (EU)*. This is equivalent to a total of around 20,000 people, and is below the threshold 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 27), Norway, Iceland and Liechtenstein. This represents a population of 506,500,000 (Eurostat 2010).

At the time of submission of the application for orphan drug designation, no satisfactory methods were authorised in the EU for the prevention of delayed graft function after renal transplantation. Several preventative measures were commonly used to reduce the risk of delayed graft function, including careful selection of the kidney donor and preservation of the kidney during transport.

This medicine is expected to be injected into patients while they are undergoing a kidney transplant. It will then accumulate in the kidney, where it is expected to work by temporarily blocking the activity of a protein called p53. During ischaemia/reperfusion injury, this protein is overactivated and causes cell death. By temporarily inactivating p53, the medicine is expected to prevent delayed graft function by delaying the induction of cell death at the time of injury, thereby allowing natural repair mechanisms to restore the normal function of the transplanted kidney.

The effects of synthetic double-stranded siRNA oligonucleotide directed against p53 mRNA 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 renal transplantation were ongoing.

At the time of submission, this medicine was not authorised anywhere in the EU for the prevention of delayed graft function after renal transplantation. Orphan designation of this medicine had been granted in the United States of America for delayed graft function after kidney transplantation.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 3 March 2010 recommending the granting of this designation.

• the seriousness of the condition,
• the existence of alternative methods of diagnosis, prevention or treatment and
• 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.