EU/03/14/1277

On 4 June 2014, orphan designation (EU/03/14/1277) was granted by the European Commission to Imperial Innovations Limited, United Kingdom, for plasmid DNA encoding the human cystic fibrosis transmembrane conductance regulator gene complexed with a non-viral, cationic lipid based gene transfer agent for the treatment of cystic fibrosis.

What is cystic fibrosis?

Cystic fibrosis is a hereditary disease that affects the cells in the lungs, and the glands in the gut and pancreas, that secrete fluids such as mucus and digestive juices. In cystic fibrosis, these fluids become thick and viscous, blocking the airways and the flow of digestive juices. This leads to long-term infection and inflammation of the lungs because of excess mucus not being cleared away, and to problems with the digestion and absorption of food, resulting in poor growth.

Cystic fibrosis is caused by abnormalities 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 0.7 in 10,000 people in the European Union (EU). This was equivalent to a total of around 36,000 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 511,100,000 (Eurostat 2014).

What treatments are available?

At the time of designation, lung infection in cystic fibrosis was mainly treated with antibiotics. Ivacaftor was authorised to correct the defect of the CFTR protein in a subgroup of patients with cystic fibrosis with the G551D mutation. Other medicines used to treat the lung disease included anti-inflammatory agents, bronchodilators (medicines that help to open up the airways in the lungs) and mucolytics (medicines that help dissolve the 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 undergo physiotherapy.

The sponsor has provided sufficient information to show that this medicine might be of significant benefit for patients with cystic fibrosis because early studies suggest that it may lead to the production of a normal CFTR protein. 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?

This medicine contains the gene (DNA) responsible for making the CFTR protein, which is combined with a lipid (fat) mixture to make a complex that can enter the cell. When given to the patient, the gene is expected to then allow these cells to produce properly functioning CFTR, resulting in normal regulation and production of mucus and digestive juices. This is expected to prevent the lung infections and the problems with absorption of nutrients characteristic of cystic fibrosis.

What is the stage of development of this medicine?

The effects of the medicine 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 cystic fibrosis were ongoing.

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 9 April 2014 recommending the granting of this designation.