EU/3/16/1702: Orphan designation for the treatment of congenital hyperinsulinism

Congenital hyperinsulinism is an inherited disorder in which the pancreas releases insulin even when it is not needed. Insulin is a hormone that helps control blood glucose (sugar) levels by driving glucose into the cells of the body. In hyperinsulinism, the increased amount of insulin causes hypoglycaemia (low blood glucose levels). The severity of congenital hyperinsulinism varies among patients and some patients develop episodes of hypoglycaemia shortly after birth. Repeated episodes of hypoglycaemia increase the risk of serious complications such as seizures (fits), mental disability, breathing difficulties and coma.

Congenital hyperinsulinism is a long-term debilitating condition because of the effects of long-term hypoglycaemia on the brain, such as mental disability and seizures.

At the time of designation, congenital hyperinsulinism affected less than 0.2 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 10,000 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, there were no satisfactory methods of treatment in the EU for congenital hyperinsulinism. Some patients were treated by surgical removal of part or all of the pancreas. Products such as diazoxide and octreotide were used to reduce insulin secretion, and glucagon injections were used in emergencies to release glucose from the liver and thereby increase blood glucose levels. However, these medicines were not authorised for use in the condition.

This medicine is a monoclonal antibody (a type of protein) that has been designed to recognise and attach to a receptor on the surface of cells, called insulin receptor. When insulin normally attaches to this receptor, it causes the cells to take up glucose from the blood. By attaching to insulin receptor, this medicine prevents insulin from attaching to it. By blocking the effects of insulin, this medicine is expected to prevent serious complications of hypoglycaemia such as fits, mental disability, breathing difficulties and coma.

The effects of the medicine have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with the medicine in patients with congenital hyperinsulinism were ongoing.

At the time of submission, the medicine was not authorised anywhere in the EU for congenital hyperinsulinism. Orphan designation of the medicine had been granted in the United States 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.