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Orphan designation

On 21 March 2016, orphan designation (EU/3/16/1622) was granted by the European Commission to BioMarin Europe Ltd., United Kingdom, for adeno-associated viral vector serotype 5 containing a B-domain deleted variant of human coagulation factor VIII gene (also called BMN 270) 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 was equivalent to a total of around 36,000 people*, and is below the ceiling for orphan designation, which is 5 people in 10,000. This isbased 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 28), Norway, Iceland and Liechtenstein. This represents a population of 513,700,000 (Eurostat 2016).

What treatments are available?

At the time of designation, medicines containing factor VIII were authorised in the EU for the treatment of haemophilia A, to replace the missing protein. However, not all patients with haemophilia A could benefit from these medicines because the immune system (the body’s natural defences) can produce ‘inhibitors’ (antibodies) against factor VIII and thereby stop the factor VIII medicine from working. In these cases, other treatments needed to be used, such as factor VIIa (the activated form of factor VII, another protein involved in blood clotting), either alone or as part of a combination treatment.

The sponsor has provided sufficient information to show that this medicine might be of significant benefit for patients with haemophilia A because results from laboratory studies show that a single administration can result in sustained production of factor VIII and restore factor VIII activity. This assumption 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 made of a virus that has been modified to contain the gene for factor VIII, which is lacking in patients with haemophilia A. After being given once to the patient as an injection into a vein, the virus is expected to carry the factor-VIII gene into the liver cells, enabling them to produce the missing factor VIII for a long period. This is expected to control the bleeding disorder.

The type of virus used in this medicine (‘adeno-associated virus’) does not cause disease in humans.

What is the stage of development of this medicine?

The effects of the medicine have been evaluated in experimental models.

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

At the time of submission, the 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 18 February 2016 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>Adeno-associated viral vector serotype 5 containing a B-domain deleted variant of human coagulation factor VIII gene</p>
Active substanceAdeno-associated viral vector serotype 5 containing a B-domain deleted variant of human coagulation factor VIII gene
Medicine Name
Disease/conditionTreatment of haemophilia A
Date of decision21/03/2016
Orphan decision numberEU/3/16/1622

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

BioMarin Europe Ltd
10 Bloomsbury Way
London WC1A 2SL
United Kingdom
Tel. +44 (0)20 7420 0800
Fax +44 (0)20 7420 0829

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.