EU/3/15/1536

On 10 August 2015, orphan designation (EU/3/15/1536) was granted by the European Commission to Plexcera Therapeutics EU Limited, Ireland, for recombinant human acid ceramidase 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 defects (‘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 51,000 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 512,900,000 (Eurostat 2015).

What treatments are available?

At the time of designation, lung infection in cystic fibrosis was mainly treated with antibiotics. Kalydeco (ivacaftor) was authorised to treat a subgroup of patients with cystic fibrosis who have certain mutations in the gene for the CFTR protein. 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 recombinant human acid ceramidase might be of significant benefit for patients with cystic fibrosis because studies in experimental models suggest that it can reduce the number of infections in patients with the 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?

In patients with cystic fibrosis, the lack of normal CFTR protein, in addition to its effects on mucus and digestive juices, also leads to build up of a fatty substance called ceramide in organs such as the lung. This build up of ceramide increases inflammation and promotes the lung infections that are symptoms of cystic fibrosis.

This medicine contains a copy of an enzyme naturally found in the body, acid ceramidase. This enzyme can break down the excess ceramide, converting it to sphingosine, a substance that helps to fight infection and reduce the growth of bacteria. This is expected to reduce the risk of dangerous chest infections in patients with the condition.

What is the stage of development of this medicine?

The effects of recombinant human acid ceramidase have been evaluated in experimental models.

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

At the time of submission, recombinant human acid ceramidase 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 July 2015 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.

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