EU/3/13/1201 - orphan designation for prevention of graft-versus-host disease
defibrotide
OrphanHuman
Overview
On 13 November 2013, orphan designation (EU/3/13/1201) was granted by the European Commission to Gentium S.p.A., Italy, for defibrotide for the prevention of graft-versus-host disease.
In January 2016, Gentium S.p.A. changed name to Gentium S.r.l.
Please note that this product was withdrawn from the Union Register of orphan medicinal products in April 2025 on request of the Sponsor.
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 or multiple myeloma (cancers 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.
At the time of designation, the number of patients at risk of GvHD was estimated to be approximately 0.23 people in 10,000 in the European Union (EU). This was equivalent to a total of around 12,000 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).
*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 512,200,000 (Eurostat 2013).
At the time of designation, several medicines were authorised in the European Union (EU) for the prevention of GvHD, such as ciclosporin 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 defibrotide might be of significant benefit for patients at risk of GvHD because preliminary clinical studies show that it may reduce the occurrence of GvHD in patients undergoing transplantation. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.
Defibrotide is expected to work by reducing formation of blood clots and increasing their breakdown in the blood. It may also protect the cells lining blood vessels, which are damaged in patients undergoing stem-cell transplantation.
The effects of defibrotide have been evaluated in experimental models.
At the time of submission of the application for orphan designation, clinical trials with defibrotide in patients at risk of GvHD were planned.
At the time of submission, defibrotide was not authorised anywhere in the EU for GvHD 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 9 October 2013 recommending the granting of this designation.
- 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.
Key facts
- Active substance
- defibrotide
- Intended use
- Prevention of graft-versus-host disease
- Orphan designation status
- Withdrawn
- EU designation number
- EU/3/13/1201
- Date of designation
- Sponsor
Gentium S.r.l.
Review of designation
The Committee for Orphan Medicinal Products reviews the orphan designation of a product if it is approved for marketing authorisation.
EMA list of opinions on orphan medicinal product designation
EMA publishes information on orphan medicinal product designation adopted by the Committee for Orphan Medicinal Products (COMP) on the IRIS online platform:
Patients' organisations
For contact details of patients’ organisations whose activities are targeted at rare diseases, see:
European Organisation for Rare Diseases (EURORDIS), a non-governmental alliance of patient organisations and individuals active in the field of rare diseases.
Orphanet, a database containing information on rare diseases, which includes a directory of patients’ organisations registered in Europe.
EU register of orphan medicines
The list of medicines that have received an orphan designation in the EU is available on the European Commission's website: