EU/3/15/1455

On 19 March 2015, orphan designation (EU/3/15/1455) was granted by the European Commission to Richardson Associates Regulatory Affairs Ltd, United Kingdom, for human plasma-derived alpha-1 proteinase inhibitor for the treatment 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 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 affected by the condition?

At the time of designation, GvHD 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 isbased 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 512,900,000 (Eurostat 2015).

What treatments are available?

At the time of designation, several medicines were authorised in the European Union (EU) for the prevention of GvHD and ciclosporin and corticosteroids were used to treat patients who developed the condition. Treatment aimed at reducing 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 human plasma-derived alpha-1 proteinase inhibitor might be of significant benefit for patients with GvHD because early results suggest that it can improve symptoms in patients who develop GvHD and who do not respond to treatment with corticosteroids and prevention with cyclosposrin. 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?

Human plasma-derived alpha-1 proteinase inhibitor is a natural protein derived from human blood that blocks the action of a group of enzymes called serine proteases. These enzymes, which include neutrophil elastase, trypsin and proteinase-3, help to break up proteins in the body and have an important role in the processes of inflammation and cell death that are triggered in GvHD. By blocking their action, the medicine is expected to improve the symptoms of the condition and reduce organ damage.

What is the stage of development of this medicine?

The effects of human plasma-derived alpha-1 proteinase inhibitor 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 GvHD were ongoing.

At the time of submission, the medicine was not authorised anywhere in the EU for GvHD or designated as an orphan medicinal product elsewhere for this condition. The medicine was available in the United States for the treatment of emphysema due to congenital deficiency of alpha-1 proteinase inhibitor (a lung disease caused by an inherited lack of the active substance in this medicine).

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 12 February 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.