EU/3/07/508

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Orphan designation

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.

For a list of the administrative updates to this public summary of opinion please refer to the PDF document below.

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).


*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.

Key facts

Product details for <p>Chimeric anti-interleukin-6 monoclonal antibody</p>
Active substanceChimeric anti-interleukin-6 monoclonal antibody
Medicine Name
Disease/conditionTreatment of Castleman's disease
Date of decision29/11/2007
OutcomePositive
Orphan decision numberEU/3/07/508

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.


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.

Life-threatening or long-term debilitating nature of the condition

The Committee for Medicinal Products for Human Use (CHMP) recommended the authorisation of Sylvant for:

‘the treatment of adult patients with multicentric Castleman’s disease who are human immunodeficiency virus (HIV) negative and human herpesvirus-8 (HHV-8) negative.’

This falls within the scope of the product’s designated orphan indication, which is: ‘treatment of Castleman’s disease’.

The COMP concluded that there had been no change in the seriousness of the condition since the orphan designation in 2007. Castleman’s disease remains a seriously debilitating and life-threatening disease, especially when the disease affects more than one lymph node, because patients are at increased risk of infections, kidney failure and certain cancers.

Prevalence of the condition

The sponsor provided information on the prevalence of Castleman’s disease from published data, which did not suggest a change in the prevalence of the condition since Sylvant’s original orphan designation.

On the basis of the information provided by the sponsor and the knowledge of the COMP, the COMP concluded that the prevalence of Castleman’s disease 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 less than 1 person in 10,000. This is equivalent to fewer than 51,000 people in the EU.

Existence of other methods of treatment

The COMP noted that, at the time of the review of the orphan designation, no treatments were authorised in the EU for patients affected by Castleman’s disease.

Conclusions

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

Related information

Sponsor’s contact details

Janssen Biologisc B.V. 
Einsteinweg 101 
2333 CB Leiden 
The Netherlands 
Tel. +31 71 5242 227 
Fax +31 71 5242 493
E-mail: ra_office@its.jnj.com

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.