EU/3/18/2114 - orphan designation for treatment in solid organ transplantation

C1 esterase inhibitor (human)

Overview

On 14 December 2018, orphan designation (EU/3/18/2114) was granted by the European Commission to Shire Pharmaceuticals Ireland Limited, Ireland, for C1 esterase inhibitor (human) for treatment in solid organ transplantation.

The sponsorship was transferred to Takeda Manufacturing Austria AG., Austria, in March 2022.

What is solid organ transplantation?

Solid organ transplantation is a surgical procedure in which a diseased organ, such as the heart, lungs, liver or kidney, is replaced with an organ from a donor.

Transplantation is a very complex procedure. During transplantation, the organ to be transplanted can become damaged because of the interruption and restoration of blood supply to the organ. In addition, graft rejection can occur after transplantation when the patient's body rejects the transplanted organ. Graft rejection is caused by the patient's immune system (the body's natural defences) recognising the transplanted graft as 'foreign' and attacking it.

These complications can be debilitating and life-threatening because they may result in the transplanted organ not working properly.

What is the estimated number of patients receiving solid organ transplants?

At the time of designation, approximately 1 in 10,000 people in the European Union (EU) were undergoing solid organ transplantation every year. This was equivalent to a total of around 52,000 people per year*, and is below the ceiling for orphan designation. 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 (European Union (EU 28), Norway, Iceland and Liechtenstein. This represents a population of 517,400,000 (Eurostat 2018).

What treatments are available?

At the time of designation, several medicines were authorised in the EU to treat graft rejection in solid organ transplantation. These include antibodies such as antilymphocyte immunoglobulin and thymoglobulin, medicines that suppress the immune process such as azathioprine, ciclosporin, mycophenolate mofetil and tacrolimus, and corticosteroids such as prednisolone or methylprednisolone.

The sponsor has provided sufficient information to show that the medicine might be of significant benefit for patients undergoing solid organ transplantation. Initial studies in patients with a kidney transplant suggest that adding the medicine to standard treatment to control rejection can improve the functioning of the transplanted organ. 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?

C1 esterase inhibitor is a natural protein extracted from human blood that helps to control the action of various enzymes and processes, including the complement system. The complement system is made up of a group of proteins in the blood that help the immune system to work. The complement system plays a critical role in the development of graft rejection. Giving additional C1 esterase inhibitor to patients after solid organ transplantation is expected to reduce the action of the complement system, and so help reduce the likelihood of the transplanted organ being rejected.

What is the stage of development of this medicine?

The effects of the medicine have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with the medicine in patients who have undergone solid organ transplantation were ongoing.

The medicine has been authorised in the EU for several years for the treatment and prevention hereditary angioedema, under the name Cinryze.

At the time of submission, the medicine was not authorised anywhere in the EU for treatment in solid organ transplantation or designated as an 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 8 November 2018 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.

EU/3/18/2114: Public summary of opinion on orphan designation: C1 esterase inhibitor (human) for treatment in solid organ transplantation

AdoptedReference Number: EMA/840912/2018

Key facts

• Active substance:
  C1 esterase inhibitor (human)
• Intended use:
  Treatment in solid organ transplantation
• Orphan designation status:
  Positive
• EU designation number:
  EU/3/18/2114
• Date of designation:
  14/12/2018
• Sponsor:

  Takeda Manufacturing Austria AG; Industriestrasse 67; Donaustadt; 1220 Vienna; Austria; Email: [e-mail]

Review of designation

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