EU/3/01/058: Orphan designation for the prevention of delayed graft function in organ transplant

Delayed graft function (DGF) is a complication that occurs in the first few days after the transplant of a solid organ, such as a kidney, when the transplanted organ does not start to work properly. DGF may be caused by events occurring after the restoration of blood flow to the transplanted organ. The damage to the organ caused by the interruption and restoration of blood flow is called ischaemia/reperfusion injury and is associated with an inflammatory reaction, characterised by the invasion of neutrophils (a type of white blood cell) into the transplanted organ. DFG is a life-threatening condition because of the risk of losing the transplanted organ.

At the time of designation, the number of patients at risk of delayed graft function in organ transplant was estimated to be approximately 1 people in 10,000 in the European Union (EU). This was equivalent to a total of around 38,000 people*, which 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.
At the time of designation, this represented a population of 378,800,000 (Eurostat 2001).

At the time of submission of application for orphan drug designation there were no satisfactory methods for the prevention of delayed graft function in organ transplant. The preventive measures to reduce delayed graft function in organ transplant consisted of donor management and organ preservation.

Repertaxin l-lysinate salt blocks the activity of of interleukin-8, a type of protein called chemokine that is responsible for the reaction of the immune system (body's natural defences) to unknown factors. IL-8 is a mediator of an inflammatory response that can occur after restoring blood flow in a transplanted organ and cause DGF. Repertaxin l-lysinate salt is suggested to inhibit the inflammatory reaction of tissue associated with restored blood flow and thus prevent the delayed graft function in organ transplant.

The effects of repertaxin L-lysinate salt were evaluated in experimental models.

At the time of submission of the application for orphan designation, no clinical trials in patients with delayed graft function in organ transplant were initiated.

Repertaxin L-lysinate salt was not marketed anywhere worldwide for the prevention of delayed graft function in organ transplant or designated as orphan medicinal product elsewhere for this condition, at the time of submission.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 18 July 2001 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 five in 10,000 people in the Community) or the 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 the quality, safety and efficacy is necessary before a product can be granted a marketing authorisation.