EU/3/16/1728

On 29 August 2016, orphan designation (EU/3/16/1728) was granted by the European Commission to Alexion Europe SAS, France, for recombinant humanised monoclonal antibody against human complement component C5a for the treatment of graft-versus-host disease.

What is graft-versus-host disease?

Graft-versus-host disease is a complication that can affect patients who have had allogeneic haematopoietic (blood) stem-cell transplantation to treat diseases of the blood such as leukaemia (a cancer of the white blood cells). The procedure involves a patient receiving stem cells from a matched donor to help restore the bone marrow, which produces new blood cells.
Graft-versus-host disease occurs when transplanted cells recognise the patient’s body as ‘foreign’ and attack the patient’s organs, such as the stomach, gut, skin and liver, leading to organ damage. The disease may happen shortly after transplantation or later on, in which case a wider range of organs can be involved.
Graft-versus-host disease is a serious and life-threatening disease with a high mortality rate.

What is the estimated number of patients affected by the condition?

At the time of designation, graft-versus-host disease affected less than 1 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 51,000 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 28), Norway, Iceland and Liechtenstein. This represents a population of 513,700,000 (Eurostat 2016).

What treatments are available?

At the time of designation, several medicines were authorised in the European Union (EU) for the treatment of graft-versus-host disease, such as ciclosporin and corticosteroids. Treatment aimed to reduce the activity of transplanted cells involved in graft-versus-host disease, thereby reducing their ability to attack the patient’s organs.
The sponsor has provided sufficient information to show that this medicine might be of significant benefit for patients with graft-versus-host disease because preliminary studies suggest that adding the medicine to standard treatments can produce good responses compared with those reported in the published literature. 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 a monoclonal antibody (a type of protein) that has been designed to attach to and block a protein of the complement system called C5a. The complement system is a group of proteins in the blood that help the immune system (the body’s natural defence system) to fight infections. It is thought that activation of the complement system plays a critical role in the development of graft-versus-host disease.
By blocking C5a, the medicine is expected to reduce inflammatory responses caused by the activation of the complement system, thus reducing the organ damage seen in graft-versus-host disease.
The medicine is made by a method known as ‘recombinant DNA technology’: it is made by cells into which a gene (DNA) has been introduced that makes them able to produce the medicine.

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 with graft-versus-host disease were ongoing.
At the time of submission, the medicine was not authorised anywhere in the EU for graft-versus-host disease 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 13 July 2016 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.