EU/3/18/2080 - orphan designation for treatment of haemophilia B

recombinant adeno-associated viral vector serotype S3 containing codon-optimised expression cassette encoding human coagulation factor IX variant

Overview

Please note that this product was withdrawn from the Union Register of orphan medicinal products in January 2024 on request of the Sponsor.

On 26 October 2018, orphan designation (EU/3/18/2080) was granted by the European Commission to Freeline Therapeutics Ltd, United Kingdom, for recombinant adeno-associated viral vector serotype S3 containing codon-optimised expression cassette encoding human coagulation factor IX variant (also known as FLT180a) for the treatment of haemophilia B.

The sponsorship was transferred to Freeline Therapeutics (Ireland) Limited Ireland in May 2019.

What is haemophilia B?

Haemophilia B is an inherited bleeding disorder caused by the lack of factor IX, a protein involved in the blood coagulation (clotting) process. Patients with haemophilia B are more prone to bleeding than normal and have poor wound healing after injury or surgery. Internal bleeding can also happen within muscles or in the joints, such as the elbows, knees and ankles. This can lead to permanent damage if it happens repeatedly.

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

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

At the time of designation, haemophilia B affected approximately 0.3 in 10,000 people in the European Union (EU). This was equivalent to a total of around 16,000 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).

 

---

* 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 517,400,000 (Eurostat 2018).

What treatments are available?

At the time of designation, medicines containing factor IX were authorised in the EU for the treatment of haemophilia B, to replace the missing protein. However, factor IX medicines did not work in some patients with haemophilia B because the immune system (the body’s natural defences) can produce ‘inhibitors’ (antibodies) against factor IX which stop the factor IX 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 the medicine might be of significant benefit for patients with haemophilia B because preliminary data show that it can increase the amount of factor IX circulating in the blood. The way the medicine works means that patients may not need or may need less frequent treatment with factor IX medicines. 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?

Patients with haemophilia B cannot make enough working factor IX because the gene for producing the clotting factor is damaged.

This medicine is made of a virus that contains copies of the gene responsible for producing factor IX. When injected into the patient, it is expected that the virus will be carried into the liver cells and start producing factor IX. It is expected that a single dose of the medicine will maintain raised levels of factor IX for a long time thereby reducing bleeding.

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 this medicine have been evaluated in experimental models.

At the time of submission of the application for orphan designation, a clinical trial with the medicine in patients with haemophilia B was ongoing.

At the time of submission, the medicine was not authorised anywhere in the EU for haemophilia B 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 13 September 2018 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/3/18/2080: Public summary of opinion on orphan designation: Recombinant adeno-associated viral vector serotype S3 containing codon-optimised expression cassette encoding human coagulation factor IX variant for the treatment of haemophilia B

Adopted Reference Number: EMA/667696/2018

Key facts

• Active substance:
  recombinant adeno-associated viral vector serotype S3 containing codon-optimised expression cassette encoding human coagulation factor IX variant
• Intended use:
  Treatment of haemophilia B
• Orphan designation status:
  Withdrawn
• EU designation number:
  EU/3/18/2080
• Date of designation:
  26/10/2018
• Sponsor:

  Freeline Therapeutics (Ireland) Limited; 6th Floor, 2 Grand Canal Square; Dublin 2; Ireland; Tel: [phone]; E-mail: [e-mail]

Review of designation

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