EU/3/04/212

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Orphan designation

On 29 July 2004, orphan designation (EU/3/04/212) was granted by the European Commission to, Gentium S.p.A, Italy, for defibrotide for the treatment of hepatic veno-occlusive disease (VOD).

For a list of the administrative updates to this public summary of opinion, please refer to the PDF document below.

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 is the estimated number of patients affected by the condition?

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).

What treatments are available?

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.

How is this medicine expected to work?

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 medicine?

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.

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/conditionTreatment of hepatic veno-occlusive disease
Date of decision29/07/2004
OutcomePositive
Orphan decision numberEU/3/04/212

Review of designation

During its meeting of 3 to 4 September 2013, the Committee for Orphan Medicinal Products (COMP) reviewed the designation EU/3/04/212 for Defitelio (defibrotide) as an orphan medicinal product for the treatment of hepatic veno-occlusive disease. The COMP assessed whether, at the time of marketing authorisation, the medicinal product still met the criteria for orphan designation. The Committee looked at the seriousness and prevalence of the condition, and the existence of other satisfactory methods of treatment. The COMP recommended that the orphan designation of the medicine be maintained.

Life-threatening or long-term debilitating nature of the condition

The Committee for Medicinal Products for Human Use (CHMP) recommended the authorisation of Defitelio for:

‘the treatment of severe hepatic veno-occlusive disease (VOD) also known as sinusoidal obstructive syndrome (SOS) in haematopoietic stem-cell transplantation (HSCT) therapy’.

This falls within the scope of the product’s designated orphan indication, which is:

‘treatment of hepatic veno-occlusive disease’.

The COMP concluded that there had been no change in the seriousness of the condition since the orphan designation in 2004. Hepatic veno-occlusive disease remains a condition that is debilitating in the long term or life threatening, particularly as it is associated with high mortality and can lead to multi-organ failure.

Prevalence of the condition

The sponsor provided new data that were not available at the time of the orphan designation in 2004. These included data from a recently published study on the proportion of patients undergoing haematopoietic stem-cell transplantation who develop hepatic veno-occlusive disease.

On the basis of the information provided by the sponsor and the knowledge of the COMP, the COMP concluded that the prevalence of hepatic veno-occlusive disease remains below the ceiling for orphan designation, which is 5 people in 10,000. At the time of the review of the orphan designation, the prevalence was estimated to be approximately 0.07 people in 10,000. This is equivalent to a total of around 3,600 people in the EU.

Existence of other satisfactory methods of treatment

The COMP noted that, at the time of the review of the orphan designation, no satisfactory treatments were authorised in the EU for patients affected by this condition.

Conclusions

Based on the data submitted and the scientific discussion within the COMP, the COMP considered that Defitelio still meets the criteria for designation as an orphan medicinal product and that Defitelio should remain in the Community Register of Orphan Medicinal Products.

Related information

Sponsor’s contact details

Gentium S.p.A
Piazza XX Settembre, 2
I-22079 Villa Guardia (CO)
Italy
Tel. +39 031 38 52 17
Fax +39 031 38 52 41
E-mail: miacobelli@gentium.it

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.