EU/3/14/1312

On 22 August 2014, orphan designation (EU/3/14/1312) was granted by the European Commission to Richardson Associates Regulatory Affairs Ltd, United Kingdom, for recombinant factor VIIa modified with three terminal repeats derived from the β chain of human chorionic gonadotropin for the treatment of congenital factor VII deficiency.

What is congenital factor VII deficiency?

Congenital factor VII deficiency is an inherited bleeding disorder that is characterised by the lack of factor VII, which is one of the proteins involved in the blood coagulation (clotting) process. Patients with factor VII deficiency are more prone to bleeding than normal and have poor wound healing after injury or surgery. Bleeding can also happen within muscles or the spaces in the joints, such as the elbows, knees and ankles.

Congenital factor VII deficiency is a debilitating disease that is life long and may be life threatening because bleeding can also happen in the brain.

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

At the time of designation, congenital factor VII deficiency affected approximately 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 isbased 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 28), Norway, Iceland and Liechtenstein. This represents a population of 511,100,000 (Eurostat 2014).

What treatments are available?

At the time of designation, medicines containing factor VII or factor VIIa (factor VII in its activated form) were authorised in the EU for the treatment of congenital factor VII deficiency. These medicines were used to replace the missing factor VII protein. Some of these medicines had to be given frequently during bleeding episodes.

The sponsor has provided sufficient information to show that this medicine might be of significant benefit for patients with congenital factor VII deficiency because early studies in experimental models indicate that it lasts longer inside the body and thus may be given less often than existing treatments. 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 copy of human factor VIIa, to which a chain made of three copies of a fragment of the ‘human chorionic gonadotropin’ (hCG) hormone has been added. In the body, the medicine is expected to replace the missing factor VII, making the patient less prone to bleeding.

Attaching the hCG chain to factor VIIa is expected to decrease the rate at which the factor VIIa is cleared from the body, allowing injections to be given less frequently than medicines that contain only factor VII or VIIa.

The medicine is made by a method known as ‘recombinant DNA technology’: it is made by cells into which a gene (DNA) has been introduced that makes them able to produce factor VIIa linked to a chain made of fragments of hCG.

What is the stage of development of this medicine?

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

At the time of submission of the application for orphan designation, no clinical trials with the medicine in patients with congenital factor VII deficiency had been started.

At the time of submission, this medicine was not authorised anywhere in the EU for congenital factor VII deficiency. Orphan designation of the medicine had been granted in the United States for the treatment and prophylaxis of bleeding episodes in patients with haemophilia A or B with inhibitors.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 10 July 2014 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.

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