EU/3/08/570

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Orphan designation

On 22 September 2008, orphan designation (EU/3/08/570) was granted by the European Commission to ProtAffin Biotechnologie AG, Austria, for recombinant human CXCL8 mutant for the prevention of delayed graft function after solid organ transplantation.

What is delayed graft function after solid organ transplantation?

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.

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

At the time of designation the population at risk of developing delayed graft function after solid organ transplantation was approximately 0.55 in 10,000 people in the European Union (EU)*. This is equivalent to a total of around 28,000 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 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 502,282,000 (Eurostat 2008).

What methods of prevention are available?

At the time of submission of the application for orphan drug designation, there were no medicinal products in the Community for the prevention of DGF after solid organ transplantation. Several preventative measures were commonly used to reduce the risk of DGF, including careful selection of the organ donor and preservation of the organ during transport.

The sponsor has provided satisfactory argumentation to justify the assumption that recombinant human CXCL8 mutant might be of potential significant benefit for the prevention of DGF after solid organ transplantation, mainly because it has a novel mechanism of action that is expected to result in better efficacy. This assumption will need to be confirmed at the time of marketing authorisation, to maintain the orphan status.

How is this medicine expected to work?

Recombinant human CXCL8 mutant is similar to the human protein CXCL8 (previously called interleukin 8). In the body, CXCL8 goes to the sites of inflammation, such as newly transplanted organs affected by ischaemia/reperfusion injury, where it attracts neutrophils. Recombinant human CXCL8 mutant replaces natural CXCL8 at the site of inflammation, but it is not able to attract neutrophils. By replacing CXCL8 at the site of the transplanted organ, recombinant human CXCL8 mutant is expected to prevent the infiltration of neutrophils into the organ, lowering the risk of DGF.

What is the stage of development of this medicine?

At the time of submission of the application for orphan designation, the evaluation of the effects of recombinant human CXCL8 mutant in experimental models was ongoing. No clinical trials in patients with solid organ transplantation had been started.

At the time of submission, recombinant human CXCL8 mutant was not authorised anywhere in the world for the prevention of DGF after solid organ transplantation, or designated as orphan medicinal product elsewhere for this condition.

According to Regulation (EC) No 141/2000 of 16 December 1999, the Committee for Orphan Medicinal Products (COMP) adopted a positive opinion on 9 July 2008 recommending the granting of the above-mentioned 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 Community) 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.

Key facts

Product details for <p>Recombinant human CXCL8 mutant</p>
Active substanceRecombinant human CXCL8 mutant
Medicine Name
Disease/conditionPrevention of delayed graft function after solid organ transplantation
Date of decision22/09/2008
OutcomePositive
Orphan decision numberEU/3/08/570

Review of designation

Sponsor’s contact details:

ProtAffin Biotechnologie AG
Impulszentrum Graz – West
Reininghausstrasse 13a
A-8020 Graz
Austria
Telephone: + 43 316 38 25 41
Telefax: + 43 316 38 25 414
E-mail: office@protaffin.com