EU/3/07/453

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Orphan designation

On 8 June 2007, orphan designation (EU/3/07/453) was granted by the European Commission to Biovitrum AB, Sweden, for recombinant fusion protein consisting of human coagulation factor IX attached to the Fc domain of human IgG1 for the treatment of haemophilia B (congenital factor IX deficiency).

The sponsorship was transferred to Biogen Idec Limited, United Kingdom, in August 2010.

Update: recombinant fusion protein consisting of human coagulation factor IX attached to the Fc domain of human IgG1 has been authorised in the EU as Alprolix since 12 May 2016.

What is haemophilia B (congenital factor IX deficiency)?

Haemophilia B is an inherited blood disorder where the body’s ability to control blood clotting (coagulation) is impaired. Patients suffering from this condition have an in-born deficiency of coagulation factor IX, which is one of the enzymes (proteins that speed up the conversion of certain substances into other substances) that help to stabilise the blood clot by mechanically linking certain big molecules to one another and thereby increasing the strength of blood clots. In affected individuals, the blood clot is not strong enough, resulting in longer bleeding time and poor wound healing in case of injury or surgery. Bleedings may also occur into muscles or joint spaces of the elbows, knees and ankles. Recurrent bleedings in the same location may lead to permanent injury of the joint. Rare, but life-threatening bleedings may occur in the central nervous system, throat or gastro-intestinal tract. Haemophilia B is chronically debilitating and may be life threatening.

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

At the time of designation, haemophilia B affected approximately 0.2 in 10,000 people in the European Union (EU)*. This is equivalent to a total of around 10,000 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 based on data from the European Union (EU 27), Norway, Iceland and Lichtenstein. This represents a population of 498,000,000 (Eurostat 2006). This estimate is based on available information and calculations presented by the sponsor at the time of the application.

What treatments are available?

Several products to treat haemophilia B (congenital factor IX deficiency) have been authorised in member states of the European Union. These products contain different levels of factor IX and aim to replace or increase the level of the deficient enzyme. Satisfactory argumentation has been submitted by the sponsor to justify the assumption that the medicinal product recombinant fusion protein consisting of human coagulation factor IX attached to the Fc domain of human IgG1 might be of potential significant benefit for the treatment of haemophilia B, because it may provide a major contribution to patient care. This assumption will have to be confirmed at the time of marketing authorisation. This will be necessary to maintain the orphan status.

How is this medicine expected to work?

Recombinant fusion protein consisting of human coagulation factor IX attached to the Fc domain of human IgG1 is a synthetic construct of the coagulation factor IX and a part from IgG antibodies (proteins that are part of the immune system). When given to a patient with haemophilia B, it is expected that the product replaces the deficient enzyme and shortens and decreases the bleedings into the surrounding tissues.. It is thought that this product is more stable than pure factor IX and therefore patients could potentially be treated less frequently with this product than with currently available products.

What is the stage of development of this medicine?

The effects of recombinant fusion protein consisting of human coagulation factor IX attached to the Fc domain of human IgG1 were evaluated in experimental models.

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

Recombinant fusion protein consisting of human coagulation factor IX attached to the Fc domain of human IgG1 was not authorised anywhere worldwide for treatment of haemophilia B nor designated as orphan medicinal product elsewhere for this condition, at the time of submission.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 12 April 2007 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>Recombinant fusion protein consisting of human coagulation factor IX attached to the Fc domain of human IgG1</p>
Active substanceRecombinant fusion protein consisting of human coagulation factor IX attached to the Fc domain of human IgG1
Medicine NameAlprolix
Disease/conditionTreatment of haemophilia B (congenital factor IX deficiency)
Date of decision08/06/2007
OutcomePositive
Orphan decision numberEU/3/07/453

Review of designation

During its meeting of 21 to 23 March 2016, the Committee for Orphan Medicinal Products (COMP) reviewed the designation EU/3/07/453 for Alprolix (eftrenonacog 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.


1 Previously known as recombinant fusion protein consisting of human coagulation factor IX attached to the Fc domain of human IgG1.

2 The 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 Alprolix 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 2007. 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 Alprolix

The COMP concluded that the claim of a significant benefit of Alprolix 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 helps patients adhere to their treatment.

Therefore, although other methods for the treatment of this condition have been authorised in the EU, the COMP concluded that Alprolix 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 Alprolix still meets the criteria for designation as an orphan medicinal product and that it should remain in the Community Register of Orphan Medicinal Products.

Sponsor’s contact details:

Biogen Idec Limited
Innovation House
70 Norden Road
Maidenhead
Berkshire, SL6 4AY
United Kingdom
Telephone: +44 1628 501 000
Telefax: +44 1628 501 010
E-mail: ukreception@biogenidec.com

Patients’ associations contact points:

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.