EU/3/07/471

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Orphan designation

On 14 September 2007, orphan designation (EU/3/07/471) was granted by the European Commission to Bio Products Laboratory, United Kingdom, for human coagulation factor X for the treatment of hereditary factor X deficiency.

Update: human coagulation factor X (Coagadex) has been authorised in the EU since 16 March 2016. Coagadex is a blood coagulation factor indicated for treatment and prophylaxis of bleeding episodes and for perioperative management in patients with hereditary factor X deficiency.

What is hereditary factor X deficiency?

Hereditary factor X deficiency is an inherited blood disorder (haemophilia), characterised by abnormal blood clotting that may result in abnormal bleeding. Human coagulation factor X is a protein that helps to stabilise the blood clot by mechanically linking certain big molecules to one another and thereby increasing the strength of blood clots. In patients with hereditary factor X deficiency, the blood clot is not strong enough, resulting in longer bleeding time and poor wound healing. Blood may seep into surrounding tissues, resulting in local pain and swelling. Bleeding may also occur in internal organs. Hereditary factor X deficiency is chronically debilitating and can be life threatening, since intracranial haemorrhage (bleeding in the brain) occurs in a significant proportion of affected individuals.

What are the methods of treatment available?

There are two main treatments used in the Community for the treatment of hereditary factor X deficiency: plasma (a mix of all proteins present in healthy blood) or a mix of purified coagulation proteins from plasma. Factor X is present in plasma in relatively low (and often unspecified) concentrations, so patients require quite high doses of the current treatments to make up for their specific deficiency of factor X. Satisfactory argumentation has been submitted by the sponsor to justify the assumption that the medicinal product human coagulation factor X might be of potential significant benefit for the treatment of hereditary factor X deficiency, because it may possibly provide a safer option to current treatments. This assumption will have to be confirmed at the time of marketing authorisation. This will be necessary to maintain the orphan status.

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

Based on the information provided by the sponsor and previous knowledge of the Committee, hereditary factor X deficiency was considered to affect less than 0.1 in 10,000 persons in the European Union, which, at the time of designation, corresponded to about 5000 persons.

*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.

How is this medicinal product expected to act?

Human coagulation factor X is expected to replace the deficient protein and thus it should prevent the longer bleeding times and the bleeding into the surrounding tissue in patients with hereditary factor X deficiency.

What is the stage of development of this medicinal product?

The evaluation of the effects of human coagulation factor X in experimental models was ongoing.

At the time of submission of the application for orphan designation, no clinical trials in patients with hereditary factor X deficiency were initiated.

Human coagulation factor X was not authorised anywhere worldwide for the treatment of hereditary factor X deficiency nor designated as orphan medicinal product elsewhere for this condition, at the time of submission.

According to Regulation (EC) No 141/2000 of 16 December 1999, the Committee for Orphan Medicinal Products (COMP) adopted on 25 July 2007 a positive opinion recommending the grant of the above-mentioned designation.

Opinions on orphan medicinal products designations are based on the following cumulative criteria:
  • the seriousness of the condition, 
  • the existence or not of alternative methods of diagnosis, prevention or treatment and 
  • either the rarity of the condition (considered to affect not more than five in ten thousand persons in the Community) or the insufficient return of development investments.

Designated orphan medicinal products are still investigational products which were considered for designation on the basis of potential activity. An orphan designation is not a marketing authorisation. As a consequence, demonstration of the quality, safety and efficacy will be necessary before this product can be granted a marketing authorisation.

Key facts

Product details for <p>Human coagulation factor X</p>
Active substanceHuman coagulation factor X
Medicine Name
Disease/conditionTreatment of hereditary factor X deficiency
Date of decision14/09/2007
OutcomePositive
Orphan decision numberEU/3/07/471

Review of designation

During its meeting of 16 to 18 February 2016, the Committee for Orphan Medicinal Products (COMP) reviewed the designation EU/3/07/471 for Coagadex (human coagulation factor X) as an orphan medicinal product for the treatment of hereditary factor X deficiency. 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 hereditary factor X deficiency. The COMP recommended that the orphan designation of the medicine be maintained*.


*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 a comparable 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 Coagadex for the ‘treatment and prophylaxis of bleeding episodes and for perioperative management in patients with hereditary factor X deficiency’.

This falls within the scope of the product’s designated orphan indication, which is: ‘treatment of hereditary factor X deficiency’.

The COMP concluded that there had been no change in the seriousness of the condition since the orphan designation in 2007. Hereditary factor X deficiency remains a condition that is debilitating in the long term and life threatening due to the risk of major bleeding, which can also happen in the brain.

Prevalence of the condition

The sponsor provided updated information on the prevalence of hereditary factor X deficiency based on data from the published scientific literature and the 2013 annual report of the World Federation of Haemophilia, as well as other registries and databases.

On the basis of the information provided by the sponsor and the knowledge of the COMP, the COMP concluded that the prevalence of hereditary factor X deficiency 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 estimated to be approximately 1 people in 10,000. This is equivalent to a total of around 51,000 people in the EU.

Existence of other methods of treatment

At the time of the review of the orphan designation, other treatments containing a mixture of human coagulation factors were authorised in several member states of the EU for the treatment and prevention of bleeding caused by deficiency of prothrombin complex coagulation factors (which include factor X deficiency).

Significant benefit of Coagadex

The COMP concluded that the claim of a significant benefit of Coagadex in hereditary factor X deficiency is justified because Coagadex is considered to be safer than currently authorised treatments. This is because, unlike other treatments, Coagadex contains only factor X and does not contain other coagulation factors that could become ‘activated’ during manufacturing and lead to the formation of blood clots.

Therefore, although other methods for the treatment of this condition have been authorised in the EU, the COMP concluded that Coagadex is of significant benefit to patients with hereditary factor X deficiency.

Conclusions

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

Related information

Sponsor’s contact details:

Bio Products Laboratory
Dagger Lane
Elstree
Hertfordshire
WD6 3BX
United Kingdom
Telephone: +44 20 82 58 22 00
Telefax: +44 20 82 58 26 08
E-mail: info@bpl.co.uk

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.