EU/3/12/1023: Orphan designation for the treatment of Barraquer-Simons syndrome

Barraquer-Simons syndrome (also known as acquired partial lipodystrophy) is a condition characterised by a lack of subcutaneous (under the skin), adipose (fatty) tissue in some parts of the body, especially the upper part.

Patients with Barraquer-Simons syndrome usually develop loss of fat during childhood or adolescence. Fat loss is gradual over a period of a few months to a few years and usually starts in the face and spreads to the neck, arms and thorax. The disease leads 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, liver cirrhosis and pancreatitis.

Barraquer-Simons syndrome is a long-term debilitating and life-threatening condition because of its severe complications, including diabetes, hypertriglyceridemia (high blood triglyceride levels) and acute pancreatitis (inflammation of the pancreas).

At the time of designation, Barraquer-Simons syndrome affected approximately 0.1 in 10,000 people in the European Union (EU). This was equivalent to a total of around 5,100 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).

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

Metreleptin is similar to a human hormone called leptin, which plays a key role in regulating body fat. In Barraquer-Simons 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.

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 Barraquer-Simons syndrome were ongoing.

At the time of submission, metreleptin was not authorised anywhere in the EU for Barraquer-Simons 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.

• 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.