EU/3/07/439 - orphan designation for treatment of cryopirin-associated periodic syndromes (FCUS, MWS, and NOMID)

Recombinant human monoclonal antibody to human IL-1beta of the IgG1/K class

Overview

Please note that this product was withdrawn from the Community Register of designated orphan medicinal poducts in December 2010 on request of the sponsor.

On 20 March 2007, orphan designation EU/3/07/439 was granted by the European Commission to Novartis Europharm Limited, United Kingdom, for recombinant human monoclonal antibody to human IL-1beta of the IgG1/K class 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).

Recombinant human monoclonal antibody to human IL-1beta of the IgG1/K class has been authorised in the EU as Ilaris since 23 October 2009.

What are cryopirin-associated periodic syndromes?

Cryopirin associated syndromes is a group of syndromes that all share the presence of alterations in the same gene and are characterized by a number of similar symptoms. The fact that the syndromes have alterations in the gene that contains the genetic information of a protein called cryopirin indicates that the expression of the alteration, even if slightly different, shares a common pathway. The syndromes are characterised by the presence of recurrent episodes of urticarial rash, fever and joint pain (arthralgia). The group includes Familial Cold Urticaria syndrome (FCAS), Muckle-Wells Syndrome (MWS) and Neonatal Onset Multisystem Inflammatory Disease (NOMID), also known as Chronic Infantile Neurological Cutaneous Articular Syndrome (CINCA). Cryopirin associated syndromes are chronically debilitating due to the recurrent episodes of the disease (fever, urticaria, arthralgia) and the development of long-term complications.

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 approximately 0.05 in 10,000 people in the European Union (EU). This was equivalent to a total of around 2,500 people*, and is below the threshold for orphan designation, which is 5 people in 10,000. This isbased on the information provided by the sponsor and the knowledge of the Committee for Orphan Medicinal Products (COMP).

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*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. At the time of designation, this represented a population of 500,300,000 (Eurostat 2007).

What treatments are available?

No satisfactory methods of treatment existed that were authorised at the time of application.

Several products with anti-inflammatory activity and others to control symptoms are not authorised for the indication but were used to treat the symptoms.

How is this medicine expected to work?

Interleukin 1 (IL-1) has been identified as one of the substances responsible for rise in body temperature and systemic inflammation. A subtype of interleukin 1 (IL1-beta) is spontaneously secreted by some blood cells (monocytes) in patients with MWS and FACS. The activity of this type of interleukin seems to be regulated by cryopirin, which is the protein that seems altered in this condition. Therefore the inhibition of IL1-beta has been proposed for treatment of the condition.

Antibodies are proteins in the body that target and bind specific structures that can be either circulating in the blood stream or on the surface of cells. The product is an antibody able to bind to IL-1 and to block its activity in the body.

What is the stage of development of this medicine?

At the time of submission of the application for orphan designation, clinical trials in patients with systemic-onset juvenile idiopathic arthritis were initiated.

Recombinant human monoclonal antibody to human IL-1beta of the IgG1/K class was not authorised anywhere worldwide for cryopirin-associated periodic syndromes or 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 7 February 2007 recommending the granting of this designation.

Update: Recombinant human monoclonal antibody to human IL-1beta of the IgG1/K class (Ilaris) has been authorised in the EU since 23 October 2009 for the treatment of cryopyrin-associated periodic syndromes (CAPS) in adults, adolescents and children aged 4 years and older with body weight above 15 kg, including:

• Muckle-Wells syndrome (MWS),
• neonatal-onset multisystem inflammatory disease (NOMID) / chronic infantile neurological, cutaneous, articular syndrome (CINCA),
• severe forms of familial cold auto-inflammatory syndrome (FCAS) / familial cold urticaria (FCU) presenting with signs and symptoms beyond cold-induced urticarial skin rash.

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.

EU/3/07/439: Recombinant human monoclonal antibody to human IL-1beta of the IgG1/K class for the treatment of cryopirin-associated periodic syndromes (Familial Cold Urticaria Syndrome (FCUS), Muckle-Wells Syndrome (MWS)...

AdoptedReference Number: EMEA/COMP/104059/2008 Rev. 3

Key facts

• Active substance:
  Recombinant human monoclonal antibody to human IL-1beta of the IgG1/K class
• Medicine name:
  Ilaris
• Intended use:
  Treatment of cryopirin-associated periodic syndromes (FCUS, MWS, and NOMID)
• Orphan designation status:
  Withdrawn
• EU designation number:
  EU/3/07/439
• Date of designation:
  20/03/2007
• Sponsor:

  Novartis Europharm Limited; Frimley Business Park; Camberley GU16 7SR; United Kingdom; Tel. [phone] (Switzerland); E-mail: [e-mail]

Review of designation

Please note that this product was withdrawn from the Community Register of designated orphan medicinal products in December 2010 on request of the sponsor, after the granting of a marketing authorisation.