EU/3/17/1859 - orphan designation for treatment of cystic fibrosis

Phosphoinositide 3-kinase gamma peptide

Overview

On 20 March 2017, orphan designation (EU/3/17/1859) was granted by the European Commission to Kither Biotech s.r.l., Italy, for phosphoinositide 3-kinase gamma peptide (also known as KIT2014) for the treatment of cystic fibrosis.

What is cystic fibrosis?

Cystic fibrosis is a hereditary 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 less than 1 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 52,000 people*, and is below the ceiling for orphan designation, which is 5 people in 10,000. This isbased on the information provided by the sponsor and the knowledge of the Committee for Orphan Medicinal Products (COMP).

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*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 515,700,000 (Eurostat 2017).

What treatments are available?

At the time of designation, Kalydeco (ivacaftor) and Orcambi (ivacaftor and lumacaftor) were authorised 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 break down mucus in the lungs). In addition, patients with cystic fibrosis were often given other types of 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 phosphoinositide 3-kinase gamma peptide might be of significant benefit for patients with cystic fibrosis because laboratory studies suggest that it can produce long-term increase in CFTR activity. 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?

Mutations of CFTR gene in cystic fibrosis cause defects in the CFTR protein, which forms channels involved in the production of fluids such as mucus and digestive juices. These channels are involved in transporting ions (charged atoms and molecules) in and out of the fluid-producing cells. When the channels are defective, transport of ions is reduced and fluid secretions become abnormally thick. The channels are activated by a substance called cyclic AMP (cAMP).

Giving the medicine by inhalation is expected to increase cAMP in the airways, thereby increasing the activity of CFTR protein channels. In this way, the medicine is expected to prevent fluid secretions in the lungs from becoming abnormally thick and so reduce the respiratory symptoms of cystic fibrosis.

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, no clinical trials with the medicine in patients with cystic fibrosis had been started.

At the time of submission, the medicine was not authorised anywhere in the EU for cystic fibrosis 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 16 February 2017 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/3/17/1859: Public summary of opinion on orphan designation: Phosphoinositide 3-kinase gamma peptide for the treatment of cystic fibrosis

AdoptedReference Number: EMA/143975/2017

Key facts

• Active substance:
  Phosphoinositide 3-kinase gamma peptide
• Intended use:
  Treatment of cystic fibrosis
• Orphan designation status:
  Positive
• EU designation number:
  EU/3/17/1859
• Date of designation:
  20/03/2017
• Sponsor:

  Kither Biotech s.r.l.; Via Nizza 52; 10126 Torino; Italy; 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.