EU/3/20/2275: Orphan designation for the treatment of insulin autoimmune syndrome

Insulin autoimmune syndrome is a condition in which the immune system (the body's defences) abnormally makes antibodies which attach to insulin and stop it from working, causing a temporary increase in blood sugar. The antibodies then start releasing the insulin, leading to a sudden rise in insulin levels that causes an excessive fall in blood sugar (hypoglycaemia).

Insulin autoimmune syndrome most commonly develops in adults. Patients have hypoglycaemia and high levels of antibodies against insulin and, over time, the condition can damage the pancreas, the gland which produces insulin. Signs of hypoglycaemia include sweating, light-headedness, weakness and tiredness. Hypoglycaemia caused by high levels of insulin can lead to effects on the brain including fits, cerebral palsy (poor coordination and muscle control) and blindness.

The disease is seriously debilitating and life-threatening because of its serious effects on the brain.

Insulin autoimmune syndrome is a condition in which the immune system (the body's defences) abnormally makes antibodies which attach to insulin and stop it from working, causing a temporary increase in blood sugar. The antibodies then start releasing the insulin, leading to a sudden rise in insulin levels that causes an excessive fall in blood sugar (hypoglycaemia).

Insulin autoimmune syndrome most commonly develops in adults. Patients have hypoglycaemia and high levels of antibodies against insulin and, over time, the condition can damage the pancreas, the gland which produces insulin. Signs of hypoglycaemia include sweating, light-headedness, weakness and tiredness. Hypoglycaemia caused by high levels of insulin can lead to effects on the brain including fits, cerebral palsy (poor coordination and muscle control) and blindness.

The disease is seriously debilitating and life-threatening because of its serious effects on the brain.

At the time of designation, insulin autoimmune syndrome affected less than 0.01 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 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).

* 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, Iceland, Liechtenstein, Norway and the United Kingdom. This represents a population of 519,200,000 (Eurostat 2020).

At the time of submission of the application for orphan drug designation, no medicine was authorised for the condition. Patients were treated with corticosteroids to reduce the production of antibodies and with medicines to reduce absorption of sugar from the digestive tract and so reduce the release of insulin from the pancreas.

The medicine is made up of a protein (called human immunoglobulin G4 fragment) attached to a copy of the natural hormone, glucagon. In the body, glucagon prevents severe hypoglycaemia but it is present only for a few minutes. It is expected that the protein attachment will allow the medicine to work for much longer so that it would need to be given just once a week.

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 insulin autoimmune syndrome were ongoing.

At the time of submission, the medicine was not authorised anywhere in the EU for the treatment of insulin autoimmune syndrome or designated as an orphan medicinal product elsewhere for this condition. It has been granted orphan designation in the EU for the treatment of congenital hyperinsulinism.

In accordance with Regulation (EC) No 141/2000, the COMP adopted a positive opinion on 19 March 2020, 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.