EU/3/15/1575

On 11 November 2015, orphan designation (EU/3/15/1575) was granted by the European Commission to Enpharma Ltd, United Kingdom, for humanised fusion protein consisting of extracellular domain of CD24 linked to IgG1 Fc domain for the prevention of graft-versus-host disease.

What is graft-versus-host disease?

Graft-versus-host disease (GvHD) is a complication that can affect patients who have received allogeneic haematopoietic (blood) stem-cell transplantation. This is a complex procedure used to treat diseases of the blood such as leukaemia (a cancer of the white blood cells), whereby a patient receives stem cells from a matched donor to help restore the bone marrow, which produces new blood cells.

In GvHD, the transplanted cells recognise the patient as ‘foreign’ and attack the patient’s organs, such as the stomach, gut, skin and liver, leading to organ damage. GvHD may happen shortly after transplantation or later on, in which case a wider range of organs can be involved.

GvHD is a serious and life-threatening disease with a high mortality rate.

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

0.3 people in 10,000 in the European Union (EU). This was equivalent to a total of around 15,000 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 at risk of developing 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 512,900,000 (Eurostat 2015).

What methods of prevention are available?

At the time of designation, several medicines were authorised in the EU for the prevention of GvHD, such as cyclosporine and antilymphocyte immunoglobulins (ATG). Treatment aimed to reduce the activity of immune cells involved in GvHD, thereby reducing their ability to attack the patient’s organs.

The sponsor has provided sufficient information to show that the medicine might be of significant benefit for patients with GvHD because it works in a different way to existing preventive treatment and results in experimental models suggest it could improve survival. 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?

Following stem-cell transplantation, damage caused by the procedure may cause the body to produce substances called cytokines. These stimulate the transplanted cells to attack the body and cause GvHD. The medicine contains a fragment of a protein called CD24, which helps to reduce the release of cytokines, thereby helping to prevent the development of GvHD.

What is the stage of development of this medicine?

The effects of this 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 at risk of GvHD were planned.

At the time of submission, the medicine was not authorised anywhere in the EU for prevention of GvHD. Orphan designation of the medicine had been granted in the United States for prevention of this condition.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 8 October 2015 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.