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Orphan designation

On 17 July 2012, orphan designation (EU/3/12/1025) was granted by the European Commission to Aptiv Solutions (UK) Limited, United Kingdom, for metreleptin for the treatment of Berardinelli-Seip syndrome.

The sponsorship was transferred to Bristol-Myers Squibb / AstraZeneca EEIG, United Kingdom, in February 2014 then to AstraZeneca AB, Sweden, in April 2014 and subsequently to Aegerion Pharmaceuticals Limited, United Kingdom, in March 2015.

The sponsorship was transferred to Aegerion Pharmaceuticals B.V., The Netherland, in November 2017.

What is Berardinelli-Seip syndrome?

Berardinelli-Seip syndrome (also known as congenital generalised lipodystrophy) is a condition characterised by a lack of adipose (fatty) tissue in the body, primarily the fat just under the skin. As a result, fats are stored elsewhere in the body, such as in the liver and muscles. Patients with the condition have a distinctive physical appearance, with an almost total absence of adipose tissue and an appearance of being very muscular.

The symptoms of Berardinelli-Seip syndrome are usually apparent from birth or early infancy, and can lead to severe complications, including high levels of fats called triglycerides circulating in the blood, insulin resistance (when the body is unable to recognise insulin, a hormone that helps regulate blood sugar levels), diabetes and an abnormal build-up of fats in organs, especially the liver.

Berardinelli-Seip syndrome is a long-term debilitating and life-threatening condition because it can lead to diabetes, hypertriglyceridemia (high blood triglyceride levels), acute pancreatitis (inflammation of the pancreas), and severe disease of major organs such as the heart, kidneys and liver.

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

At the time of designation, Berardinelli-Seip syndrome affected approximately 0.05 in 10,000 people in the European Union (EU). This was equivalent to a total of around 2,500 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 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 509,000,000 (Eurostat 2012).

What treatments are available?

At the time of designation, no methods were authorised in the EU for the treatment of Berardinelli-Seip syndrome. Patients with the condition were advised to follow a low-fat diet.

How is this medicine expected to work?

Metreleptin is similar to a human hormone called leptin, which plays a key role in regulating body fat. In Berardinelli-Seip syndrome, metreleptin is expected to increase fat breakdown in the blood, muscles and liver, and improve insulin function, thereby correcting some abnormalities in patients with this condition such as insulin resistance. However, the medicine is not expected to restore adipose tissue.

Metreleptin is made by a method known as ‘recombinant DNA technology’: it is made by bacteria that have received a gene (DNA) which makes them able to produce metreleptin.

What is the stage of development of this medicine?

The effects of metreleptin have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with metreleptin including patients with Berardinelli-Seip syndrome were ongoing.

At the time of submission, metreleptin was not authorised anywhere in the EU for Berardinelli-Seip syndrome. Orphan designation of metreleptin had been granted in the United States of America for metabolic disorders secondary to lipodystrophy.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 13 June 2012 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.

Name Language First published Last updated
EU/3/12/1025: Public summary of opinion on orphan designation: Metreleptin for the treatment of Berardinelli-Seip syndrome (English only) 2012-08-31 2015-05-13

Key facts

Product details for <p>Metreleptin</p>
Active substanceMetreleptin
Medicine Name
Disease/conditionTreatment of Berardinelli-Seip syndrome
Date of decision17/07/2012
Orphan decision numberEU/3/12/1025

Review of designation

The Committee for Orphan Medicinal Products reviews the orphan designation of a product if it is approved for marketing authorisation.

Sponsor’s contact details

Aegerion Pharmaceuticals B.V.
Atrium Building, 8th Floor
Strawinskylaan 3127
1077 ZX Amsterdam
The Netherlands
Tel: +31 (0)88 560 9950

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.