EU/3/08/604 - orphan designation for prevention of ischaemia/reperfusion injury associated with solid organ transplantation

recombinant human minibody against complement component C5 fused with RGD-motif

Overview

On 20 January 2009, orphan designation (EU/3/08/604) was granted by the European Commission to Adienne S.r.l., Italy, for recombinant human minibody against complement component C5 fused with RGD-motif for the prevention of the ischaemia/reperfusion injury associated with solid organ transplantation.

In January 2014, ADIENNE S.r.l. changed name to ADIENNE S.r.l.S.U.

For a list of the administrative updates to this public summary of opinion please refer to the PDF document below.

Please note that this product was withdrawn from the Community Register of designated Orphan Medicinal Products in April 2019 on request of the Sponsor.

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

Ischaemia and reperfusion injury are problems that can occur during an organ 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 is called ischaemia, and, if prolonged, can cause damage to the organ because of the lack of oxygen and nutrients. When the graft is attached to the recipient's blood circulation, the restoration of blood supply to the organ can cause inflammation and damage to the organ (reperfusion injury). These processes increase the risk of the graft not working or being rejected by the recipient. Because ischaemia/reperfusion injury associated with solid organ transplantation is a threat to the survival of the graft, it is a life-threatening condition.

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

At the time of designation, ischaemia/reperfusion injury associated with solid organ transplantation affected less than 1 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than absolute number of patients with a thousand separator e.g. 10,000 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).

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*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. At the time of designation, this represented a population of 504,800,000 (Eurostat 2009).

What methods of prevention are available?

To prevent problems during organ transplant, the grafts are usually stored in cold conditions in solutions that reduce the effects of ischaemia. Satisfactory argumentation has been submitted by the sponsor to justify the assumption that recombinant human minibody against complement component C5 fused with RGD-motif might be of potential significant benefit for the prevention of ischaemia/reperfusion injury associated with solid organ transplantation, mainly because it has a new mechanism of action that could limit the damage to, and improve the function of transplanted grafts. 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 expected to work by limiting the activation of the 'complement' system and decreasing the damage caused to the graft. Complement is part of the immune system (the body's natural defences) and plays a role in the inflammation and damage caused by ischaemia and reperfusion injury.

The medicine is made up of two elements that have been fused together:

• 'minibody' (an engineered antibody) that has been designed to attach itself to one of the proteins of the complement system called component C5;
• a 'RGD-motif molecule' which has been design to attach itself to the cells lining blood vessels.

The medicine is used on the graft while it is being stored. The medicine attaches itself to the blood vessels via the RGD-motif molecule. Once the graft is transplanted and the blood supply is connected, the minibody part of the medicine can attach itself to component C5 in the blood vessels if the complement system is activated. This may limit the activation of the complement system within the transplanted organ.

What is the stage of development of this medicine?

The evaluation of the effects of recombinant human minibody against complement component C5 fused with RGD-motif in experimental models was ongoing.

At the time of submission of the application for orphan designation, no clinical trials in patients receiving grafts at risk of developing ischaemia/reperfusion injury associated with solid organ transplantation had been started.

At the time of submission, recombinant human minibody against complement component C5 fused with RGD-motif was not authorised anywhere in the world for ischaemia/reperfusion injury associated with solid organ transplantation or designated as 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 5 November 2008 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;
• 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.

EU/3/08/604: Public summary of positive opinion for orphan designation of recombinant human minibody against complement component C5 fused with RGD-motif for prevention of the ischaemia/reperfusion injury associated with...

Adopted Reference Number: EMA/COMP/609861/2008 Rev.2

Key facts

• Active substance:
  recombinant human minibody against complement component C5 fused with RGD-motif
• Intended use:
  Prevention of ischaemia/reperfusion injury associated with solid organ transplantation
• Orphan designation status:
  Withdrawn
• EU designation number:
  EU/3/08/604
• Date of designation:
  20/01/2009
• Sponsor:

  ADIENNE S.r.l.S.U.