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Orphan designation

On 29 July 2004, orphan designation (EU/3/04/211) was granted by the European Commission to Gentium S.p.A, Italy, for defibrotide for the prevention of hepatic veno-occlusive disease (VOD).

A marketing authorisation application for defibrotide for prevention of hepatic veno-occlusive disease was withdrawn in July 2013.

In January 2016, Gentium S.p.A. changed name to Gentium S.r.l.

What is hepatic veno-occlusive disease?

Hepatic veno-occlusive disease (VOD) is a disease of the liver in which the small vessels are destroyed. This can occur following liver transplantation but also as an adverse reaction to certain medicines. Examples of the latter one are chemotherapeutic agents (drugs used to kill cancer cells or used in certain circumstances to eliminate cells of the body’s defence system) or medicines containing specific proteins called antibodies used to target abnormal cells in certain diseases such as acute myeloid leukaemia. Hepatic veno-occlusive disease (VOD) is characterised by painful enlargement of the liver (hepatomegaly), yellowing of the skin and eyes caused by excess bile products in the blood (jaundice), excess fluid in the abdomen (ascites) and weight gain due to fluid retention by the body. 

What are the methods of prevention available?

No satisfactory methods exist that were authorised at the time of application. 

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

According to the information provided by the sponsor, the risk of hepatic veno-occlusive disease was considered to affect about 51,000 persons in the European Union. 

*Disclaimer: For the purpose of the designation, the number of patients affected by the condition is estimated and assessed based on data from the European Union (EU 25), Norway, Iceland and Lichtenstein. This represents a population of 459,700,000 (Eurostat 2004). This estimate is based on available information and calculations presented by the sponsor at the time of the application.

How is this medicinal product expected to act?

Defibrotide is expected to act by preventing the clotting (thrombosis) in the blood vessels (antithrombotic activity) or by stimulating the dissolution of the clot (thrombolysis). 

What is the stage of development of this medicinal product?

The effects of defibrotide were evaluated in experimental models. At the time of submission of the application for orphan designation, clinical trials in patients to prevent hepatic veno-occlusive disease were ongoing. The medicinal product was not marketed anywhere worldwide for hepatic veno-occlusive disease at the time of submission. Orphan designation of defibrotide was granted in the United States for the treatment of hepatic veno-occlusive disease. 
According to Regulation (EC) No 141/2000 of 16 December 1999, the Committee for Orphan Medicinal Products (COMP) adopted on 16 June 2004 a positive opinion recommending the grant of the above-mentioned designation.

Opinions on orphan medicinal products designations are based on the following cumulative criteria:
  • the seriousness of the condition, 
  • the existence or not of alternative methods of diagnosis, prevention or treatment and 
  • either the rarity of the condition (considered to affect not more than five in ten thousand persons in the Community) or the insufficient return of development investments. 

Designated orphan medicinal products are still investigational products which were considered for designation on the basis of potential activity. An orphan designation is not a marketing authorisation. As a consequence, demonstration of the quality, safety and efficacy will be necessary before this product can be granted a marketing authorisation.

Key facts

Product details for <p>Defibrotide</p>
Active substanceDefibrotide
Medicine Name
Disease/conditionPrevention of hepatic veno-occlusive disease
Date of decision29/07/2004
Orphan decision numberEU/3/04/211

Review of designation

Sponsor’s contact details:

Gentium S.r.l.
Piazza XX Settembre, 2
I-22079 Villa Guardia (CO)
Tel. +39 031 5373 200
Fax +39 031-5373 784

Patients’ organisations

For contact details of patients’ organisations whose activities are targeted at rare diseases, see:

  • Orphanet, a database containing information on rare diseases, which includes a directory of patients’ organisations registered in Europe;
  • European Organisation for Rare Diseases (EURORDIS), a non-governmental alliance of patient organisations and individuals active in the field of rare diseases.