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.
- 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 is below the threshold for orphan designation which is 5 in 10,000 people, and is equivalent to a total of around 50,000 people. This is based on the information provided by the sponsor and 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 based on data from the European Union (EU 27), Norway, Iceland and Liechtenstein. This represents a population of 502,282,000 (Eurostat 2008).
- 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.
|Name||Language||First published||Last updated|
|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 solid organ transplantation||(English only)||29/06/2009||18/11/2010|
|Active substance||Recombinant human minibody against complement component C5 fused with RGD-motif|
|Disease/condition||Prevention of the ischaemia/reperfusion injury associated with solid organ transplantation|
|Date of decision||19/01/2009|
|Orphan decision number||EU/3/08/604|
Review of designation
Sponsor’s contact details:
via Broseta, 64/B
Telephone: +39 035 4329 793
Telefax: +39 035 258 672
For contact details of patients’ organisations whose activities are targeted at rare diseases see:
- Orphanet, a database containing information on rare diseases which includes a directory of patients’ organisations registered in Europe.
- European Organisation for Rare Diseases (EURORDIS), a non-governmental alliance of patient organisations and individuals active in the field of rare diseases.