EU/3/04/235 - orphan designation for treatment of type B extreme insulin resistance syndrome

recombinant human insulin-like growth factor-I / recombinant human insulin-like growth factor binding protein-3

Overview

Please note that this product was withdrawn from the Community Register of designated Orphan Medicinal Products in March 2007 on request of the sponsor.

On 20 October 2004, orphan designation (EU/3/04/235) was granted by the European Commission to Insmed Incorporated, United Kingdom, recombinant human insulin-like growth factor-I/recombinant human insulin-like growth factor binding protein-3 (rhIGF-I/rhIGFBP-3) for the treatment of Type B extreme insulin resistance syndrome.

The sponsorship was transferred to Insmed Europe Limited, United Kingdom in December 2006.

What is Type B extreme insulin resistance syndrome?

Insulin is a hormone that helps the body use the sugar in the food as fuel. Because of the action of insulin, sugar does not normally accumulate in the blood in excess. In order to show its effects, insulin binds to insulin-receptors on the cell surface. Type B extreme resistance insulin syndrome is a condition in which the immune system (body's natural defences) blocks insulin and prevents its normal functions. Patients suffering from this disease have antibodies (proteins of the immune system) that bind to insulin receptors, occupy them and prevent insulin from binding and function normally.
Type B extreme insulin resistance syndrome occurs in middle age. Typically, Type B occurs in association with other autoimmune diseases (diseases caused by the body own's defence system attacking normal tissue), such as systemic lupus erythematosus, Hashimoto's thyroiditis, and Sjogren syndrome, alopecia areata, vitiligo, arthritis, nephritis, primary biliary cirrhosis Hodgkin's disease and ataxia-telangiectasia. Type B extreme insulin resistance syndrome is a chronically debilitating condition.

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

At the time of designation, Type B extreme insulin resistance syndrome affected not more than 0.02 in 10,000 people in the European Union (EU)*. This is equivalent to a total of not more than 920 people, and is below the ceiling for orphan designation, which is 5 people in 10,000. This is based 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 based on data from the European Union (EU 25), Norway, Iceland and Liechtenstein. This represents a population of 459,700,000 (Eurostat 2004).

What treatments are available?

Although no satisfactory methods existed that were authorised at the time of application, various treatments were used including high doses of insulin, oral antidiabetics, or medicines that are able to reduce the immune defence (immunesupressors) such as azathioprine, cyclosporin A and cyclophosphamide.

How is this medicine expected to work?

Recombinant human insulin-like growth factor-I/recombinant human insulin-like growth factor binding protein-3 (rhIGF-I/rhIGFBP-3) is a complex formed by two components: recombinant human insulin-like growth factor and its binding protein. As rhIGF-I is able to induce metabolic activities of insulin through IGF-I receptor, it is expected that the product will be able to bypass defects in the function of insulin receptor occupied by antibodies that are present in patients with Type B extreme insulin resistance syndrome.

What is the stage of development of this medicine?

The effects of rh IGF-I/rh IGF-IBP3 had been evaluated in experimental models.

At the time of submission of the application for orphan designation, no clinical trials in patients with Type B extreme insulin resistance were initiated.

Recombinant human insulin-like growth factor-I/recombinant human insulin-like growth factor binding protein-3 (rhIGF-I/rhIGFBP-3) had been granted orphan drug status in the United States on December 9, 2003 for the treatment of Extreme Insulin Resistance Syndrome (Type A syndrome , Rbason-Mendenhall syndrome, Leprechaunism and Type B syndrome).

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 9 September 2004 recommending the granting of this designation.

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/3/04/235: Public summary of positive opinion for orphan designation of recombinant human insulin-like growth factor-I/recombinant human insulin-like growth factor binding protein-3 for treatment of Type B extreme insu...

Adopted Reference Number: EMEA/COMP/77803/2004 Rev. 1

Key facts

• Active substance:
  • recombinant human insulin-like growth factor-I
  • recombinant human insulin-like growth factor binding protein-3
• Intended use:
  Treatment of type B extreme insulin resistance syndrome
• Orphan designation status:
  Withdrawn
• EU designation number:
  EU/3/04/235
• Date of designation:
  20/10/2004
• Sponsor:

  Insmed Europe Ltd; Compass House; Vision Park,; Chivers Way; Histon; Cambridge CB 4 9AD; United Kingdom; Telephone: + 44 1223 25 77 43; Telefax: + 44 1223 25 78 00; E-mail: [e-mail]