EU/3/20/2316 - orphan designation for prevention of haemolytic uraemic syndrome

protein-based delivery vector carrying a DNA payload encoding an RNA-guided nuclease that targets stx genes of Shiga toxin-producing Escherichia coli

Overview

On 21 August 2020, orphan designation EU/3/20/2316 was granted by the European Commission to Eligo Bioscience, France, for protein-based delivery vector carrying a DNA payload encoding an RNA-guided nuclease that targets stx genes of Shiga toxin-producing Escherichia coli for the prevention of haemolytic uraemic syndrome.

What is haemolytic uraemic syndrome?

Haemolytic uraemic syndrome (HUS) is a disorder characterised by three main signs: haemolysis (destruction of red blood cells), thrombocytopenia (a decrease in the number of platelets, components that help the blood to clot) and kidney failure. HUS can lead to formation of blood clots that damage small vessels supplying the organs and may cause problems in the brain and nervous system, and damage to other organs such as the heart, gut and kidneys.

HUS is often associated with infections with Escherichia coli bacteria that produce a toxin called Shiga toxin (Shiga toxin-producing E. coli or STEC). The toxin damages the lining of blood vessels, triggering the symptoms of the disease. STEC-associated HUS primarily affects young children who catch the infection mostly through contaminated food sources.

HUS is a long-lasting and life-threatening disease mainly because of the risk of kidney failure and complications affecting the brain and other organs.

What is the estimated number of patients at risk of developing the condition?

At the time of designation, the number of patients at risk of developing HUS was estimated to be approximately 0.24 in 10,000 people in the European Union (EU). This was equivalent to a total of around 12,000 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).

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*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).

What methods of prevention are available?

At the time of designation, no satisfactory methods of prevention for HUS were authorised in the EU. The medicine Soliris was authorised to treat patients affected by non-infectious forms of the condition (atypical HUS), while patients who developed STEC-related HUS were managed with supportive treatment. Transfusions of red blood cells and platelets were given as needed, as well as medicines to manage complications such as seizures (fits). Dialysis (a blood clearance technique) was used if the disease progressed to kidney failure. Some patients needed a kidney transplant.

How is this medicine expected to work?

This medicine contains genetic material (DNA) which, once in the cells, leads to the production of an enzyme that will target and eliminate the Escherichia coli that produce the Shiga toxin causing the symptoms of the disease. By eliminating the bacteria, the medicine is expected to reduce the production of the toxin and thereby prevent HUS.

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 this medicine in experimental models was ongoing.

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

At the time of submission, the medicine was not authorised anywhere in the EU for the prevention of HUS or designated as an orphan medicinal product elsewhere for this condition.

In accordance with Regulation (EC) No 141/2000, the COMP adopted a positive opinion on 16 July 2020, 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/3/20/2316: Public summary of opinion on orphan designation: Protein-based delivery vector carrying a DNA payload encoding an RNA-guided nuclease that targets stx genes of Shiga toxin-producing Escherichia coli

Adopted Reference Number: EMADOC-628903358-2743

Key facts

• Active substance:
  protein-based delivery vector carrying a DNA payload encoding an RNA-guided nuclease that targets stx genes of Shiga toxin-producing Escherichia coli
• Intended use:
  Prevention of haemolytic uraemic syndrome
• Orphan designation status:
  Positive
• EU designation number:
  EU/3/20/2316
• Date of designation:
  21/08/2020
• Sponsor:

  Eligo Bioscience; 111 Avenue De France; Paris; 75013; France

  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.