EU/3/11/896: Orphan designation for the treatment of cystic fibrosis

Cystic fibrosis is a hereditary disease that affects the production of secretions such as mucus in the body. It mainly affects the lungs and the digestive system (gut). Cystic fibrosis is caused by abnormalities in a gene called 'cystic fibrosis transmembrane conductance regulator' (CFTR). The CFTR gene is responsible for the production of the CFTR protein. This protein regulates the production of mucus and digestive juices by acting as a channel to allow the movement of salt and water in and out of cells in the lungs and other tissues.

In patients with cystic fibrosis, there is the production of thick mucus in the lungs and a reduced production of digestive juices from the pancreas (an organ near the stomach). This leads to long-term infection and inflammation of the lungs and problems with the digestion and absorption of food resulting in poor growth.

Cystic fibrosis is a long-lasting and life-threatening disease because it leads to lung tissue damage and infections that result in breathing and heart problems as well as problems with the pancreas resulting in poor absorption of food and diabetes.

At the time of designation, cystic fibrosis affected approximately 1.3 in 10,000 people in the European Union (EU)*. This is equivalent to a total of around 66,000 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).

*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 27), Norway, Iceland and Liechtenstein. This represents a population of 506,300,000 (Eurostat 2011).

At the time of submission of the application for orphan drug designation, lung infection in cystic fibrosis was mainly treated with antibiotics. 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 it works in a different way to existing treatments, and early studies indicate that it might improve the outcome of patients with this condition when used in combination with other treatments. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

Patients with cystic fibrosis have been shown to have a reduced amount of 'lamellar bodies' in their lungs. Lamellar bodies are small fat-containing particles that are thought to play important roles in the lung, such as keeping the small airways open, improving the transport of mucus and debris and helping defend against infection and inflammation.

The medicine is expected to work by mimicking the missing lamellar bodies. It is made up of small particles called 'vesicles', containing the same fats found in lamellar bodies and is intended to be delivered to patient's airways with a nebuliser (a special machine that changes the solution into an aerosol that the patient can breathe in).

The effects of the medicine 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, 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 10 June 2011 recommending the granting of this designation.

• 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.