EU/3/04/237 - orphan designation for treatment of Rabson-Mendenhall 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Please note that this product was withdrawn from the Community Register of designated Orphan Medicinal Products in March 2007 on request of the sponsor.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 21 October 2004, orphan designation (EU/3/04/237) 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 the Rabson Mendenhall syndrome.

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

What is Rabson Mendehall syndrome?

Rabson Mendehall syndrome is an inherited condition characterized by extreme insulin resistance. 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. In this disease insulin is not able to function properly because insulin receptors have a defect. Symptoms of the Rabson-Mendenhall syndrome also include abnormalities of the head and face, abnormalities of the teeth and nails, and skin abnormalities such as acanthosis nigricans, a skin disorder characterized by abnormally increased coloration and velvety thickening (hyperkeratosis).

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

At the time of designation, Rabson Mendenhall 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 27), Norway, Iceland and Liechtenstein. This represents a population of 502,282,000 (Eurostat 2008).

What treatments are available?

No satisfactory methods exist that were authorised at the time of application for the treatment of Rabson Mendenhall syndrome. Treatments such as high fibre diet, and substances such as guar gum, and oral antidiabetics (e.g tolbutamide) or insulin were used. Treatment consisting of surgically removing the pituitary gland, and administering a substance called growth hormone were used in the most severe cases.

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 the defects in the insulin receptor or insulin signalling pathway that are present in patients with Rabson Mendnhall syndrome.

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 the Rabson Mendenhall syndrome 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/3/04/237: 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 Rabson Mendnhal...

AdoptedReference Number: EMEA/COMP/77791/2004 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 Rabson-Mendenhall syndrome
• Orphan designation status:
  Withdrawn
• EU designation number:
  EU/3/04/237
• 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]