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Orphan designation

On 10 October 2012, orphan designation (EU/3/12/1052) was granted by the European Commission to Novo Nordisk A/S, Denmark, for humanised monoclonal IgG4 antibody against tissue-factor-pathway inhibitor for the treatment of haemophilia A.

What is haemophilia A?

Haemophilia A is an inherited bleeding disorder that is caused by the lack of factor VIII, which is one of the proteins involved in the blood coagulation (clotting) process. Patients with haemophilia A are more prone to bleeding than normal and have prolonged bleeding after injury or surgery. Bleeding can also happen within muscles or the spaces in the joints, such as the elbows, knees and ankles. This can lead to permanent injury if it happens repeatedly.

Haemophilia A is a debilitating disease that is life-long and may be life threatening because bleeding can happen in the brain, the spinal cord or the gut.

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

At the time of designation, haemophilia A affected approximately 0.7 in 10,000 people in the European Union (EU)*. This is equivalent to a total of around 35,000 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).

What treatments are available?

At the time of submission of the application for orphan drug designation, medicines containing factor VIII were authorised in the EU for the treatment of haemophilia A, to replace the missing protein. Some patients needed other treatments, such as medicines containing other substances involved in blood clotting.

The sponsor has provided sufficient information to show that the medicine ‘humanised monoclonal IgG4 antibody against tissue-factor-pathway inhibitor’ might be of significant benefit for patients with haemophilia A because it works in a different way to existing treatments, and early studies in experimental models show that it might prevent bleeding in patients with this condition. In addition, the medicine will also be available as a solution for subcutaneous (under the skin) injection, which will be more convenient to use than currently authorised treatments, which are given as injections into a vein. These assumptions will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

How is this medicine expected to work?

This medicine is a monoclonal antibody (a type of protein) that has been designed to recognise and attach to a molecule in the body called ‘tissue-factor-pathway inhibitor’ (TFPI). TFPI blocks the production of factor Xa, a protein central to the clotting process. The production of factor Xa is controlled by two separate pathways, one involving factor VIII, the other involving TFPI. By attaching to TFPI, this medicine is expected to block its action, resulting in a prolonged production of factor Xa. This is expected to increase the ability of the blood to clot and help control the bleeding disorder, bypassing the need for factor VIII.

What is the stage of development of this medicine?

The effects of humanised monoclonal IgG4 antibody against tissue-factor-pathway inhibitor have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with the medicine including patients with haemophilia A were ongoing.

At the time of submission, this medicine was not authorised anywhere in the EU for haemophilia A 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 12 September 2012 recommending the granting of this designation.

Opinions on orphan medicinal product designations are based on the following three criteria:
  • 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

Product details for <p>Humanised monoclonal IgG4 antibody against tissue-factor-pathway inhibitor</p>
Active substanceHumanised monoclonal IgG4 antibody against tissue-factor-pathway inhibitor
Medicine Name
Disease/conditionTreatment of haemophilia A
Date of decision10/10/2012
Orphan decision numberEU/3/12/1052

Review of designation

The Committee for Orphan Medicinal Products reviews the orphan designation of a product if it is approved for marketing authorisation.

Sponsor’s contact details:

Novo Nordisk A/S
Novo Alle 1,
2880 Bagsvaerd
Telephone: +45 30759347
Telefax: +45 44436740

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.