EU/3/09/723

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Orphan designation

On 4 February 2010, orphan designation (EU/3/09/723) was granted by the European Commission to CSL Behring GmbH, Germany, for recombinant fusion protein linking human coagulation factor IX with human albumin (also known as rIX-FP) for the treatment of haemophilia B.

Update: recombinant fusion protein linking human coagulation factor IX with human albumin has been authorised in the EU as Idelvion since 11 May 2016.

More information on Idelvion can be found in the European public assessment report (EPAR).

What is haemophilia B?

Haemophilia B is an inherited bleeding disorder that is caused by the lack of a substance called factor IX. Factor IX is one of the human proteins involved in the blood clotting process. Patients with haemophilia B 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, which can lead to permanent injury if it happens repeatedly.

Haemophilia B is a debilitating disease that is lifelong and may be life threatening if bleeding happens in the brain, spinal cord, throat or gut.

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

At the time of designation, haemophilia B affected approximately 0.1 in 10,000 people in the European Union (EU)*. This is equivalent to a total of around 5,000 people, and is below the threshold for orphan designation, which is 5 people in 10,000. This is based on the information provided by the sponsor and 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 27), Norway, Iceland and Liechtenstein. This represents a population of 504,800,000 (Eurostat 2009).

What treatments are available?

At the time of submission of the application for orphan designation, medicines containing factor IX were authorised in the EU for the treatment of haemophilia B. These medicines replace the missing protein. In some patients, other treatments were also needed, such as medicines containing other substances involved in blood clotting such as factor VIIa.

The sponsor has provided sufficient information to show that recombinant fusion protein linking human coagulation factor IX with human albumin might be of significant benefit for patients with haemophilia B because the medicine is expected to be given less often than currently used 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?

The medicine is made of a copy of human factor IX, which is attached to albumin, a protein that acts as a carrier. In the body, the medicine is expected to replace the missing factor IX, making the patient less prone to bleeding. Attaching albumin to factor IX is expected to decrease the rate at which the factor IX is cleared from the body, allowing more time between injections than for medicines that contain only factor IX.

The medicine is made by a method known as ‘recombinant DNA technology’: it is made by a cell that has received a gene (DNA) that makes it able to produce factor IX linked to albumin.

What is the stage of development of this medicine?

The effects of recombinant fusion protein linking human coagulation factor IX with human albumin have been evaluated in experimental models.

At the time of submission of the application for orphan designation, no clinical trials with the designated product in patients with haemophilia B had been started.

At the time of submission, recombinant fusion protein linking human coagulation factor IX with human albumin 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 3 December 2009 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 Community) 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>Recombinant fusion protein linking human coagulation factor IX with human albumin</p>
Active substanceRecombinant fusion protein linking human coagulation factor IX with human albumin
Medicine Name
Disease/conditionTreatment of haemophilia B
Date of decision04/02/2010
OutcomePositive
Orphan decision numberEU/3/09/723

Review of designation

During its meeting of 21 to 23 March 2016, the Committee for Orphan Medicinal Products (COMP) reviewed the designation EU/3/09/723 for Idelvion (albutrepenonacog alfa1)as an orphan medicinal product for the treatment of haemophilia B. The COMP assessed whether, at the time of marketing authorisation, the medicinal product still met the criteria for orphan designation. The Committee looked at the seriousness and prevalence of the condition, and the existence of other methods of treatment. As other methods of treatment are authorised in the European Union (EU), the COMP also considered whether the medicine is of significant benefit to patients with haemophilia B. The COMP recommended that the orphan designation of the medicine be maintained2.


1Previously known as recombinant fusion protein linking human coagulation factor IX with human albumin.

2The maintenance of the orphan designation at time of marketing authorisation would, except in specific situations, give an orphan medicinal product 10 years of market exclusivity in the EU. This means that in the 10 years after its authorisation similar products with the same therapeutic indication cannot be placed on the market.

Life-threatening or long-term debilitating nature of the condition

The Committee for Medicinal Products for Human Use (CHMP) recommended the authorisation of Idelvion for ‘treatment and prophylaxis of bleeding in patients with haemophilia B (congenital factor IX deficiency)’.

This falls within the scope of the product’s designated orphan indication, which is ‘treatment of haemophilia B’.

The COMP concluded that there had been no change in the seriousness of the condition since the orphan designation in 2010. Haemophilia B remains a condition that is debilitating in the long term and life threatening because it can lead to bleeding in the brain and spinal cord and from the throat and the gut.

Prevalence of the condition

The sponsor provided updated information on the prevalence of haemophilia B based on data from the 2013 World Federation of Hemophilia Global Survey.

On the basis of the information provided by the sponsor and the knowledge of the COMP, the COMP concluded that the prevalence of haemophilia B remains below the ceiling for orphan designation, which is 5 people in 10,000. At the time of the review of the orphan designation, the prevalence was still estimated to be approximately 0.2 people in 10,000. This is equivalent to a total of around 10,000 people in the EU.

Existence of other methods of treatment

At the time of the review of the orphan designation, injectable medicines containing factor IX were authorised in the EU to treat haemophilia B. Medicines containing factor VII were authorised for use in patients who developed inhibitors (antibodies) that stopped factor IX medicines from working.

Significant benefit of Idelvion

The COMP concluded that the claim of a significant benefit of Idelvion in haemophilia B is justified because this medicine is given less frequently (once every 1 to 2 weeks) than other currently authorised treatments (which are given twice a week). This results in improved quality of life for patients and reduces the need of using a central venous access port (a tube placed in a large vein to allow for frequent access to the bloodstream).

Therefore, although other methods for the treatment of this condition have been authorised in the EU, the COMP concluded that Idelvion is of significant benefit to patients affected by haemophilia B.

Conclusions

Based on the data submitted and the scientific discussion within the COMP, the COMP considered that Idelvion still meets the criteria for designation as an orphan medicinal product and that it should remain in the Community Register of Orphan Medicinal Products.

Related information

Sponsor’s contact details

CSL Behring GmbH
Emil-von-Behring-Str. 76
35041 Marburg
Germany
Tel. +49 6421 3912
Fax +49 6421 3985
E-mail: rIX-FP@cslbehring.com

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.