EU/3/11/946)

On 11 January 2012, orphan designation (EU/3/11/946) was granted by the European Commission to Astellas Pharma Europe B.V., the Netherlands, for recombinant homodimer of the human annexin V for the prevention of ischaemia/reperfusion injury associated with solid organ transplantation.

What is ischaemia/reperfusion injury associated with solid organ transplantation?

Ischaemia and reperfusion injury are problems that can occur to transplant organs as a result of being preserved during the time between donation and transplant. In the course of a transplant, the organ to be transplanted (the ‘graft’) needs to survive outside the body with no blood supply for a short while. This decrease in blood supply, if prolonged, can cause damage to the organ because of the lack of oxygen and nutrients, a condition called ischaemia. When the graft is attached to the recipient’s blood circulation, the restoration of blood supply to the organ (reperfusion) can cause inflammation and damage to the organ, known as reperfusion injury. These processes increase the risk of the graft not working or being rejected by the recipient.

Because ischaemia/reperfusion injury in solid organ transplantation impairs the functioning of the graft, it is a life-threatening condition for the recipient of the graft.

What is the estimated number of patients at risk of developing the condition?

At the time of designation, the number of patients at risk of ischaemia/reperfusion injury associated with solid organ transplantation was estimated to be approximately 0.6 people in 10,000 in the European Union (EU)*. This is equivalent to a total of around 30,000 people, which 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 27), Norway, Iceland and Liechtenstein. This represents a population of 506,300,000 (Eurostat 2011).

What methods of prevention are available?

At the time of designation, methods used to reduce the effects of ischaemia included storage of the organ in cold conditions in special preservation solutions. Two such solutions were authorised for organ preservation in some countries of the EU at the time of designation.

The sponsor has provided sufficient information to show that recombinant homodimer of the human annexin V might be of significant benefit for patients at risk of ischemia/reperfusion injury associated with solid organ transplantation because it works in a different way to existing methods and early studies indicate it may improve the prevention of this condition. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

How is this medicine expected to work?

This medicine is made of a protein, annexin V, which is expected to work as an anticoagulant (a substance that prevents the blood from clotting). Since the formation of blood clots can occur during ischemia/reperfusion injury, this medicine is expected to prevent damage to the graft.

The medicine is produced by a method known as ‘recombinant DNA technology’: it is made by a bacterium that has received a gene (DNA), which makes it able to produce the medicine.

What is the stage of development of this medicine?

The effects of recombinant homodimer of the human annexin V have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with recombinant homodimer of the human annexin V in patients at risk of ischaemia/reperfusion injury associated with solid organ transplantation were ongoing.

At the time of submission, this medicine was not authorised anywhere in the EU for the prevention of ischaemia/reperfusion injury associated with solid organ transplantation. Orphan designation of the medicine had been granted in the United States of America for the prevention of ischaemia/reperfusion injury associated with solid organ transplantation.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 9 November 2011 recommending the granting of this designation.

Opinions on orphan medicinal product designations are based on the following three criteria:

• 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.

The Committee for Orphan Medicinal Products reviews the orphan designation of a product if it is approved for marketing authorisation.