EU/3/04/236 - orphan designation for treatment of type A 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Please note that this product was withdrawn from the Community Register of designated orphan medicinal products in May 2007 on request of the sponsor.

On 21 October 2004, orphan designation (EU/3/04/236) was granted by the European Commission to Insmed Incorporated, United Kingdom, for 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 A extreme resistance insulin syndrome.

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

What is Type A extreme insulin resistance syndrome?

Insulin is a hormone that helps the body break down the sugar in the food to use as energy. Normally, sugar does not accumulate in the blood in excess. Insulin binds to insulin-receptors on the surface of cells and the sugar is then taken up by the cells. Type A extreme insulin resistance syndrome is due to an inherited condition where the insulin receptors are not produced normally. This means that insulin cannot properly bind to the receptors causing sugar to accumulate in the blood. In patients, this appears as high levels of insulin in the blood (hyperinsulinaemia), increased colouration and “velvety” thickening (acanthosis nigricans) of the skin and development of male-like features in females (virilisation). Type A 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 A extreme insulin resistance syndrome affected approximately 0.02 in 10,000 people in the European Union (EU)*. This is equivalent to a total of around 900 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 Lichtenstein. This represents a population of 459,700,000 (Eurostat 2004). This estimate is based on available information and calculations presented by the sponsor at the time of the application.

What treatments are available?

Several methods of treatment such as insulin, oral antidiabetic medicines alone or in combination have been used although there exist no authorised therapeutic method.

How is this medicine expected to work?

The product may work by going around the abnormal pathway represented by insulin and its defective receptor. 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 parts: recombinant human insulin-like growth factor and its binding protein. Recombinant human insulin-like growth factor shares structural and functional similarities with insulin. It can produce its insulin-like functions by binding to its own receptors although it can bind to insulin receptors. The role of the binding protein is to reduce the insulin-like side effects such as hypoglycaemia, in addition to other functions as carrier of insulin-like growth factor-I.

What is the stage of development of this medicine?

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

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

RhIGF-I/rhIGFBP-3 has been granted orphan drug status in the United States for the treatment of Growth Hormone Insensitivity Syndrome and the treatment of Extreme Insulin Resistance Syndrome. Recombinant human insulin-like growth factor-I/recombinant human insulin-like growth factor binding protein-3 (rhIGF-I/rhIGFBP-3) has 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/3/04/236: Public summary of opinion on orphan designation: Recombinant human insulin-like growth factor-I/recombinant human insulin-like growth factor binding protein-3 for the treatment of Type A extreme insulin resi...

Adopted Reference Number: EMA/COMP/77786/2004

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 A extreme insulin resistance syndrome
• Orphan designation status:
  Withdrawn
• EU designation number:
  EU/3/04/236
• Date of designation:
  21/10/2004
• 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]

Review of designation

Please note that this product was withdrawn from the Community Register of designated orphan medicinal products in May 2007 on request of the sponsor, before a marketing authorisation had been granted.