EU/3/18/2022 - orphan designation for treatment of congenital hyperinsulinism

Glucagon analogue linked to a human immunoglobulin Fc fragment

Overview

On 25 May 2018, orphan designation (EU/3/18/2022) was granted by the European Commission to Hanmi Europe Limited, United Kingdom, for glucagon analogue linked to a human immunoglobulin Fc fragment (also known as HM15136) for the treatment of congenital hyperinsulinism.

The sponsorship was transferred to JVM Europe B.V., Netherlands, in April 2019.

What is congenital hyperinsulinism?

Congenital hyperinsulinism is an inherited disorder in which the body releases insulin even when it is not needed. Insulin is a hormone that helps control levels of blood glucose (sugar) by increasing absorption of glucose into the cells of the body. In hyperinsulinism, the increased amount of insulin makes too much glucose enter the cells and 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.

What is the estimated number of patients affected by the condition?

At the time of designation, congenital hyperinsulinism affected approximately 1 in 10,000 people in the European Union (EU). This was equivalent to a total of less than 52,000 people^{*,/sup>, 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 517,400,000 (Eurostat 2018).

What treatments are available?

At the time of designation, no medicines were authorised in the EU for the treatment of congenital hyperinsulinism. Products such as diazoxide and octreotide were used to reduce insulin release, and glucagon and glucose were used in emergencies to increase blood glucose levels short term in patients with congenital hyperinsulinism. However, these medicines were not authorised specifically for use in this condition.

How is this medicine expected to work?

The medicine contains a copy of the hormone glucagon, which is naturally produced by the body. It acts like natural glucagon and releases glucose from the liver, which increases blood glucose levels thereby reducing the symptoms of the disease.

The glucagon in the medicine is combined with a type of protein called immunoglobulin G4 fragment, which helps the hormone stay active in the body for longer. This allows the medicine to be given less frequently than natural glucagon.

What is the stage of development of this medicine?

At the time of submission of the application for orphan designation, the evaluation of the effects of the medicine in experimental models was ongoing.

At the time of submission of the application for orphan designation, no clinical trials with the medicine in patients with congenital hyperinsulinism had been started.

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 19 April 2018 recommending the granting of this designation.

Opinions on orphan medicinal product designations are based on the following three criteria:

• 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.

EU/3/18/2022: Public summary of opinion on orphan designation: Glucagon analogue linked to a human immunoglobulin Fc fragment for the treatment of congenital hyperinsulinism

Reference Number: EMA/271839/2018

Key facts

• Active substance:
  Glucagon analogue linked to a human immunoglobulin Fc fragment
• Intended use:
  Treatment of congenital hyperinsulinism
• Orphan designation status:
  Positive
• EU designation number:
  EU/3/18/2022
• Date of designation:
  25/05/2018
• Sponsor:

  JVM Europe B.V.; Niels Bohrweg 6; Lelystad; Flevoland; 8218 MD; The Netherlands; Tel. [phone]; E-mail: [e-mail]

Review of designation

The Committee for Orphan Medicinal Products reviews the orphan designation of a product if it is approved for marketing authorisation.