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Orphan designation

On 10 July 2007, orphan designation (EU/3/07/456) was granted by the European Commission to Regeneron UK Limited, United Kingdom, for rilonacept for the treatment of cryopirin-associated periodic syndromes (familial cold urticaria syndrome (FCUS), Muckle-Wells syndrome (MWS) and neonatal onset multisystem inflammatory disease (NOMID), also known as chronic infantile neurological cutaneous articular syndrome (CINCA)).

What are cryopirin-associated periodic syndromes?

Cryopirin is a protein encoded by the CIASI/NAPL3 gene that is involved in the activation of a signalling compound called IL-1β. This compound is very important for the inflammatory process (the body’s response to an infection). In patients affected by cryopirin-associated periodic syndromes, the CIASI/NAPL3 gene is defective, which leads to an excessive activity of the cryopirin protein and subsequently to an excessive signalling by IL-1β. Symptoms of the resulting systemic (covering the entire body) inflammation include periods of high fever, rash, headaches, fatigue and joint problems. In the long run the condition can cause further complications such as deafness. Cryopirin-associated periodic syndromes are chronically debilitating.

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

At the time of designation, cryopirin-associated periodic syndromes (Familial Cold Urticaria Syndrome (FCUS), Muckle-Wells Syndrome (MWS), and Neonatal Onset Multisystem Inflammatory Disease (NOMID), also known as Chronic Infantile Neurological Cutaneous Articular Syndrome (CINCA)) affected less than 0.05 in 10,000 in 10,000 people in the European Union (EU)*. This is equivalent to a total of fewer than 2,500 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 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?

There are no medicinal products authorised for the treatment of the condition in the Community. Severe flares of the disease can sometimes be treated symptomatically with anti-inflammatory products.

How is this medicine expected to work?

Rilonacept is structurally similar to the IL-1β receptor (the protein that IL-1β interacts with and through which it signals). Rilonacept binds to IL-1β and thus inhibits it the harmful activity of IL-1β.

What is the stage of development of this medicine?

The effects of rilonacept have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials in patients with cryopirin-associated periodic syndromes were ongoing.

Rilonacept was not authorised anywhere worldwide for the treatment of cryopirin-associated periodic syndromes 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 a positive opinion on 31 May 2007 recommending the granting of the above-mentioned designation.

Update: Rilonacept (Arcalyst) has been authorised in the EU since 23 October 2009 for the treatment of cryopyrin-associated periodic syndromes (CAPS) with severe symptoms, including familial cold auto-inflammatory syndrome (FCAS) and Muckle-Wells syndrome (MWS), in adults and children aged 12 years and older.

Opinions on orphan medicinal products designations are based on the following cumulative 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 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>Rilonacept</p>
Active substanceRilonacept
Medicine NameRilonacept Regeneron
Disease/conditionTreatment of cryopirin-associated periodic syndromes
Date of decision10/07/2007
Orphan decision numberEU/3/07/456

Review of designation

Sponsor’s contact details:

Regeneron UK Limited
40 Bank Street
Canary Wharf
London, E14 5DS
United Kingdom
Telephone: + 44 20 7519 70 59
Telefax: + 44 20 7519 70 59

Patients’ associations contact points:

NICMD: The National Information Centre for Metabolic Diseases
Climb Building
176 Nantwich Road
Crewe CW2 6BG
United Kingdom
Telephone: +44 845 241 2174
Telefax: +44 845 241 2174

Associazione Italiana Febbri Periodiche
San Marco 4781
30124 Venezia
Telephone: +39 346 41 08 714
Telefax: +39 178 27 25 891