EU/3/14/1430 - orphan designation for treatment of congenital factor VII deficiency

adeno-associated viral vector serotype 8 containing the human factor-VII gene

Overview

On 15 January 2015, orphan designation (EU/3/14/1430) was granted by the European Commission to Professor Edward G. Tuddenham, United Kingdom, for adeno-associated viral vector serotype 8 containing the human factor-VII gene for the treatment of congenital factor VII deficiency.

The sponsorship was transferred to UCL Research Limited, Ireland, in February 2020.

What is congenital factor VII deficiency?

Congenital factor VII deficiency is an inherited bleeding disorder that is characterised by the lack of factor VII, one of the proteins involved in blood clotting. 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 occur 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 0.06 in 10,000 people in the European Union (EU). This was equivalent to a total of around 3,000 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 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 might improve the body's production of factor VII. 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?

The medicine is made of a virus that contains the gene responsible for making factor VII, the protein lacking in patients with congenital factor VII deficiency. After being injected into the patient, the virus is expected to carry the factor VII gene into the liver cells, enabling them to produce continuously the missing factor VII, thus restoring normal blood clotting and avoiding the need of regular treatment with factor VII medicines.

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?

At the time of submission of the application for orphan designation, the evaluation of the effects of the medicine in experimental models was ongoing.

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

At the time of submission, the medicine was not authorised anywhere in the EU for congenital factor VII deficiency 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 11 December 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.

EU/3/14/1430: Public summary of opinion on orphan designation: Adeno-associated viral vector serotype 8 containing the human factor-VII gene for the treatment of congenital factor VII deficiency

Adopted Reference Number: EMA/COMP/10146/2015

Key facts

• Active substance:
  adeno-associated viral vector serotype 8 containing the human factor-VII gene
• Intended use:
  Treatment of congenital factor VII deficiency
• Orphan designation status:
  Positive
• EU designation number:
  EU/3/14/1430
• Date of designation:
  15/01/2015
• Sponsor:

  UCL Research Limited;

Review of designation

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