EU/3/06/425 - orphan designation for atypical haemolytic uraemic syndrome

Complement factor H

Overview

Please note that this product was withdrawn from the Community Register of designated orphan medicinal products in June 2012 on request of the sponsor.

On 26 January 2007, orphan designation (EU/3/06/425) was granted by the European Commission to Laboratoire Français du Fractionnement et des Biotechnologies (LFB), France, for complement factor H for the treatment of atypical haemolytic uraemic syndrome (aHUS) associated with an inherited abnormality of the complement system.

The sponsor's name changed to Laboratoire Français du Fractionnement et des Biotechnologies (LFB) S.A. in April 2008.

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

What is atypical haemolytic uraemic syndrome associated with an inherited abnormality of the complement system?

Haemolytic uraemic syndrome (HUS) is a disorder marked by kidney failure, haemolysis (destruction of red blood cells), thrombocytopoenia (platelet deficiency), coagulation defects, and variable nervous system symptoms. This disorder is most common in children, and typically occurs after a gastrointestinal infection, often one caused by a specific subtype of the bacterium E.coli. It has also been associated with other gastrointestinal infections, including those caused by Shigella and Salmonella bacteria.

Its less frequent form, atypical HUS (a-HUS), has been associated with other conditions, such as some non-enteric infections or diseases of the immune system, and in some instances with inherited abnormalities of the complement system. It is the latter condition which is the subject of the orphan drug designation. The complement system is a group of proteins in the blood, which help the immune system (antibodies and immune cells) in fighting infections.
Atypical HUS associated with an inherited abnormality of the complement system can occur in both children and adults. Multiple members of one family may be affected. Due to an inherited (genetic) defect, the production of complement proteins is disrupted, resulting in a-HUS. A-HUS can be chronic, or recur at intervals (relapsing form).

The condition is life-threatening and chronically debilitating, in particular due to kidney failure and a high likelihood of kidney transplant rejection.

What is the estimated number of patients affected by the condition?

At the time of designation, atypical Haemolytic Uraemic Syndrome associated with an inherited abnormality of the complement system affected less than 0.1 in 10,000 people in the European Union (EU). This was equivalent to a total of around 5,000 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).

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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 27), Norway, Iceland and Liechtenstein. At the time of designation, this represented a population of 500,300,000 (Eurostat 2007).

What are the methods of treatment available?

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

The current treatment is supportive. Transfusions of packed red cells and platelets are given as needed. Kidney dialysis may be indicated.

Plasmapheresis, also called plasma exchange (or passage of the blood plasma through a filter) may be performed, although its role is not completely clear. In plasmapheresis, the blood plasma (the portion that does not contain cells, but does contain antibodies) is removed and replaced with fresh (donated) plasma.

How is this medicinal product expected to act?

Complement factor H is a major regulator of the complement system. It is normally produced in the liver, and is present in the blood. In genetic abnormalities of the complement system, supplementation of purified complement factor H is thought to alleviate the disease, by restoring a normal capacity to regulate complement activity.

What is the stage of development of this medicinal product?

The evaluation of the effects of complement factor H in experimental models is ongoing. At the time of submission of the application for orphan designation, no clinical trials in patients with a-HUS associated with an inherited abnormality of the complement system were initiated.

Complement factor H was not authorised anywhere worldwide for a-HUS associated with an inherited abnormality of the complement system or designated as orphan medicinal product elsewhere for this condition, at the time of submission.

According to Regulation (EC) No 141/2000 of 16 December 1999, the Committee for Orphan Medicinal Products (COMP) adopted on 6 December 2006 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.

EU/3/06/425: Public summary of positive opinion for orphan designation of complement factor H for the treatment of atypical haemolytic uraemic syndrome associated with an inherited abnormality of the complement system

Adopted Reference Number: EMEA/COMP/521235/2006 Rev.3

Key facts

• Active substance:
  Complement factor H
• Intended use:
  Atypical haemolytic uraemic syndrome
• Orphan designation status:
  Withdrawn
• EU designation number:
  EU/3/06/425
• Date of designation:
  27/01/2007
• Sponsor:

  Laboratoire Français du Fractionnement et des Biotechnologies (LFB) S.A.; 3 avenue des Tropiques; BP80097; 91943 Courtaboeuf Cedex; France; Tel. [phone]; Fax [phone]; E-mail: [e-mail]