EU/3/04/212: Orphan designation for the treatment of 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.

At the time of designation, hepatic veno-occlusive disease (VOD) affected not more than 0.4 in 10,000 people in the European Union (EU). This was equivalent to a total of 19,000 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 25), Norway, Iceland and Liechtenstein. At the time of designation, this represented a population of 464,200,000 (Eurostat 2004).

No satisfactory methods exist that were authorised at the time of application. Supportive measures are aimed at maintaining an adequate functioning of the liver and include dietary restriction of salt and liquids, administration of medicines called diuretics that help removing fluids from the body.

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).

The effects of defibrotide were evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials in patients with hepatic veno-occlusive disease (VOD) 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.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 16 June 2004 recommending the granting of this designation.

Update: Defibrotide (Defitelio) has been authorised in the EU since 18 October 2013 for the treatment of severe hepatic veno-occlusive disease (VOD) also known as sinusoidal obstructive syndrome (SOS) in haematopoietic stem-cell transplantation (HSCT) therapy.

It is indicated in adults and in adolescents, children and infants over 1 month of age.

• 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.