EU/3/19/2189 - orphan designation for treatment of cystic fibrosis

gallium citrate

Overview

On 21 August 2019, orphan designation EU/3/19/2189 was granted by the European Commission to Clinical Network Services (NL) B.V, the Netherlands, for gallium citrate for the treatment of cystic fibrosis.

In August 2020, Clinical Network Services (NL) B.V.changed name to Scendea (NL) B.V.

The sponsorship was transferred to Marcello Menapace in July 2021.

What is cystic fibrosis?

Cystic fibrosis is an inherited disease that affects the secretion of fluids from cells in the lungs and from the glands in the gut and pancreas. In cystic fibrosis, these fluids become thick, blocking the airways in the lungs and the flow of digestive juices in the gut and pancreas. This leads to inflammation and long-term infection of the lungs because of the build-up of thick mucus, and to poor growth and nutrition because of problems with the digestion and absorption of food.

Cystic fibrosis is caused by changes (mutations) in a gene that makes a protein called 'cystic-fibrosis transmembrane conductance regulator' (CFTR), which is involved in regulating the production of mucus and digestive juices.

Cystic fibrosis is a long-term debilitating and life-threatening disease because it severely damages the lung tissue, leading to problems with breathing and to recurrent chest infections.

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

At the time of designation, cystic fibrosis affected approximately 1 in 10,000 people in the European Union (EU). This was equivalent to a total of around 52,000 people¹, 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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¹Disclaimer: 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 518,400,000 (Eurostat 2019).

What treatments are available?

At the time of designation, Kalydeco (ivacaftor), Orkambi (ivacaftor and lumacaftor) and Symkevi (tezacaftor and ivacaftor) were authorised in the EU to treat patients with cystic fibrosis who have certain mutations in the gene for CFTR. Lung infection in cystic fibrosis was mainly treated with antibiotics. Other medicines used to treat the lung disease included anti-inflammatory medicines, bronchodilators (medicines that help to open up the airways in the lungs) and mucolytics (medicines that help break down mucus in the lungs). In addition, patients with cystic fibrosis were often given other medicines such as pancreatic enzymes (substances that help to digest and absorb food) and food supplements. They were also advised to exercise and to have physiotherapy.

The sponsor has provided sufficient information to show that the medicine might be of significant benefit for patients with cystic fibrosis. Laboratory data showed that adding the medicine to colistin, an authorised antibiotic for treating cystic fibrosis, can increase effectiveness against bacteria called Pseudomonas aeruginosa, which cause long-term infection in patients with this condition. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

How is this medicine expected to work?

Patients with cystic fibrosis often suffer from P. aeruginosa infections. Bacteria such as P. aeruginosa need iron to grow and multiply, to produce copies of their DNA (genetic material) and to protect themselves against damage known as ‘oxidative stress’. This medicine contains gallium, which attaches to iron-binding proteins on bacterial cells instead of iron. This means the bacteria do not get enough iron and cannot function and grow properly. This restriction in bacterial growth is expected to reduce the symptoms of bacterial infection in patients with cystic fibrosis.

What is the stage of development of this medicine?

The effects of gallium citrate have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with gallium citrate in patients with cystic fibrosis were ongoing.

At the time of submission, gallium citrate was not authorised anywhere in the EU for the treatment of cystic fibrosis. Orphan designation of gallium citrate had been granted in the United States for the treatment of lung infections in patients with cystic fibrosis.

In accordance with Regulation (EC) No 141/2000, the COMP adopted a positive opinion on 18 July 2019, 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/3/19/2189: Public summary of positive opinion for orphan designation of gallium citrate for the treatment of cystic fibrosis

Reference Number: EMADOC-628903358-1309

Key facts

• Active substance:
  gallium citrate
• Intended use:
  Treatment of cystic fibrosis
• Orphan designation status:
  Positive
• EU designation number:
  EU/3/19/2189
• Date of designation:
  21/08/2019
• Sponsor:

  Marcello Menapace; Via Due Giugno 6 ; 20094 Corsico (MI) ; Italy ; 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.