EU/3/04/238 - orphan designation for treatment of leprechaunism

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Please note that this product was withdrawn from the Community Register of designated Orphan Medicinal Products in March 2007 on request of the sponsor.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 21 October 2004, orphan designation (EU/3/04/238) 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 leprechaunism.

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

What is leprechaunism?

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 cells' surface. Leprechaunism is an inherited disorder in which insulin cannot bind to insulin- receptors and therefore cannot function properly. Due to this defect there is a delay in the normal development occurring before and after birth. This delay is associated with characteristic facial features (resembling that of 'leprechauns', the ancient elves in the Irish folk traditions), reduction of the fatty and muscular tissues in the body. Signs of virilisation (male-like characters) are often observed in little girls. Imbalance in the sugar (glucose) level in the blood is also present. The condition is life-threatening.

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

At the time of designation, leprechaunism 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/ fewer 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 Lichtenstein. This represents a population of 459,700,000 (Eurostat 2004).

What treatments are available?

There was no authorised method of treatment at the time of designation. Treatment with recombinant human insulin-like growth factor (IGF) I had been used.

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 insulin receptor or insulin signalling pathway that are present in patients with Leprechaunism. Therefore the product is expected to reduce the symptoms and the growth retardation seen in these patients.

What is the stage of development of this medicine?

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

At the time of submission of the application for orphan designation, no clinical trials in patients with leprechaunism 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/3/04/238: 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 the treatment of leprechaunism

Adopted Reference Number: EMEA/COMP/77797/2004 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 leprechaunism
• Orphan designation status:
  Withdrawn
• EU designation number:
  EU/3/04/238
• 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]