EU/3/07/508 - orphan designation for treatment of Castleman's disease

Chimeric anti-interleukin-6 monoclonal antibody (siltuximab)

Overview

On 30 November 2007, orphan designation (EU/3/07/508) was granted by the European Commission to Centocor, B.V., The Netherlands, for chimeric-anti-interleukin 6 monoclonal antibody for the treatment of Castleman's disease.

Centocor B.V. changed its name to Janssen Biologisc B.V. in July 2011.

The sponsorship was transferred to Janssen-Cilag International N.V., Belgium, in June 2013.

Chimeric-anti-interleukin 6 monoclonal antibody has been authorised in the EU as Sylvant since 22 May 2014.

This medicine is now known as siltuximab.

The sponsorship was transferred to EUSA Pharma (Netherlands) B.V, in July 2019.

The sponsor’s address was updated in August 2021.

What is Castleman's disease?

Castleman's disease is a disorder of the lymphatic system (lymph nodes and lymphatic vessels, where, among other things, fluids and cells of the immune system circulate). In affected patients, for an unknown reason, cells in lymphoid tissue start proliferating causing primarily abnormally large lymph nodes, often with benign tumours. In a majority of cases, the disease is located to only one lymph node, but in some cases the disease is systemic (affects the entire body) and affects several lymph nodes as well as other organs in the body. Affected patients have an increased risk of infections, kidney failure and certain cancers. Castleman's disease is chronically debilitating and life threatening, especially for patients with more than one affected lymph node.

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

At the time of designation, Castleman's disease affected less than 1 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 50,000 people*, and is below the ceiling 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?

There are no medicinal products authorised for the treatment of Castleman's disease in the Community. In some mild cases of the disease, affected lymph nodes can be removed surgically. However, in most cases, only symptomatic treatment is available.

How is this medicine expected to work?

Chimeric-anti-interleukin 6 monoclonal antibody is a protein molecule designed to bind and neutralise a compound called interleukin 6 in the body. Interleukin 6 belongs to a family of compounds called cytokines, which mediate processes in the immune system. It has been shown that interleukin 6 itself promotes growth and survival of cells. It is thought that chimeric-anti-interleukin 6 monoclonal antibody will inhibit interleukin 6 from binding to its receptor on the lymphatic cells and thus inhibiting the excessive growth of these cells in affected patients.

What is the stage of development of this medicine?

The effects of Chimeric-anti-interleukin 6 monoclonal antibody were evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials in patients with Castleman's disease were ongoing.

Chimeric-anti-interleukin 6 monoclonal antibody was not authorised anywhere worldwide for the treatment of Castleman's disease, at the time of submission.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 10 October 2007 recommending the granting of this designation.

Update: chimeric-anti-interleukin 6 monoclonal antibody (Sylvant) has been authorised in the EU since 22 May 2014 for the treatment of adult patients with multicentric Castleman's disease (MCD who are human immunodeficiency virus (HIV) negative and human herpesvirus-8 (HHV-8) negative.

More information on Sylvant can be found in the European public assessment report (EPAR) on the Agency's website.

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.

EU/3/07/508: Public summary of positive opinion for orphan designation of chimeric-anti-interleukin 6 monoclonal antibody for the treatment of Castleman’s disease

AdoptedReference Number: EMEA/COMP/147287/2008 Rev.2

Key facts

• Active substance:
  Chimeric anti-interleukin-6 monoclonal antibody (siltuximab)
• Medicine name:
  Sylvant
• Intended use:
  Treatment of Castleman's disease
• Orphan designation status:
  Positive
• EU designation number:
  EU/3/07/508
• Date of designation:
  30/11/2007
• Sponsor:

  Recordati Netherlands B.V.; Beechavenue 54; Schipol-Rijk; Noord-Holland; 1119 PW; Netherlands

  E-mail: [e-mail];

Review of designation

During its meeting of 8 to 9 April 2014, the Committee for Orphan Medicinal Products (COMP) reviewed the designation EU/3/07/508 for Sylvant (siltuximab, previously known as chimeric-anti-interleukin 6 monoclonal antibody) as an orphan medicinal product for the treatment of Castleman's disease. 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 satisfactory methods of treatment. The COMP recommended that the orphan designation of the medicine be maintained¹.

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¹The 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.