EU/3/16/1711: Orphan designation for the treatment of familial partial lipodystrophy

Familial partial lipodystrophy is an inherited condition in which fat is lost from some parts of the body and it accumulates in other parts. Patients with familial partial lipodystrophy have normal body fat distribution until early childhood, but during or after puberty they lose fat progressively from the arms and legs, and from the front of the belly and chest. Many patients (especially women) have accumulation of fat in the face, neck and within the belly.

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 to regulate blood sugar levels), diabetes and an abnormal build-up of fats in organs, especially the liver and heart.

Familial partial lipodystrophy is a life-threatening and long-term debilitating condition because of its severe complications including diabetes, high blood triglyceride levels, acute pancreatitis (inflammation of the pancreas) and heart disease.

At the time of designation, familial partial lipodystrophy affected less than 0.1 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 5,000 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 28), Norway, Iceland and Liechtenstein. This represents a population of 513,700,000 (Eurostat 2016).

At the time of designation, no satisfactory methods were authorised in the EU for the treatment of familial partial lipodystrophy. Patients with the condition were advised to follow a low-fat diet and to exercise. Medicines that increase the effect of insulin (e.g. metformin) and lipid-lowering medicines (e.g. statins, fibrates) can improve the condition but don't significantly lower triglyceride levels.

This medicine is an 'antisense oligonucleotide', a short piece of genetic material that has been designed to attach to genetic material in the cell responsible for producing the apoC-III protein. This reduces production of apoC-III, which is often raised in lipodystrophy patients. Since apoC-III regulates triglyceride levels in the body, reducing its production is expected to reduce triglyceride levels and improve the symptoms of the disease.

The effects of volanesorsen sodium have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with volanesorsen sodium in patients with familial partial lipodystrophy were ongoing.

At the time of submission, volanesorsen sodium was not authorised anywhere in the EU for familial partial lipodystrophy or designated as an orphan medicinal product elsewhere for this condition.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 16 June 2016 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.