EU/3/15/1589: Orphan designation for the treatment of neonatal diabetes

Neonatal diabetes is a form of diabetes that is diagnosed in the first 6 months of life. This condition is distinct from the more common type 1 diabetes (which occurs later).

Signs and symptoms are those that typically occur with poor blood sugar control including thirst, frequent urination, dehydration and, in severe cases, a harmful build-up of acid (ketoacidosis). Infants with neonatal diabetes may also suffer nervous system disorders which may cause muscle weakness and convulsions (fits).

Neonatal diabetes is life threatening and debilitating in the long term because of the symptoms caused by high blood sugar levels and the risk of ketoacidosis.

At the time of designation, neonatal diabetes 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).

* 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 512,900,000 (Eurostat 2015).

At the time of the orphan designation, insulin was authorised in the EU for use in neonatal diabetes.

The sponsor has provided sufficient information to show that glibenclamide might be of significant benefit for patients with neonatal diabetes because early studies indicate that patients treated with glibenclamide may not need to be treated with insulin or may need less insulin. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

Glibenclamide is authorised for treating type 2 diabetes. It works on insulin-producing cells in the pancreas by attaching to a KATP channel, which controls the release of insulin. In many newborn babies with neonatal diabetes, the cells in the pancreas produce insulin but they are not able to release it into the blood. The lack of insulin in the blood causes symptoms of diabetes. Glibenclamide's effect on the KATP channel restores the cells' ability to release insulin into the blood. Glibenclamide is also thought to make the rest of the body respond more effectively to insulin. These effects are expected to reduce the symptoms of neonatal diabetes.

The effects of glibenclamide 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 neonatal diabetes were ongoing.

At the time of submission, the medicine was not authorised anywhere in the EU for neonatal diabetes 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 12 November 2015 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.