EU/3/19/2150: Orphan designation for the treatment of 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.

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 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 28), Norway, Iceland and Liechtenstein. This represents a population of 518,400,000 (Eurostat 2019).

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 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 the medicine might be of significant benefit for patients with cystic fibrosis. Laboratory studies showed that the medicine may improve the movement of chloride particles across the cell membrane and thus help to regulate the production of fluids from cells. In addition, the medicine could be used in patients in whom the CFTR protein is completely lacking, for whom no treatment is authorised.

This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

This medicine contains genetic material (mRNA) responsible for making the CFTR protein, which is enclosed in tiny fatty particles that allow the genetic material to enter into cells. When the medicine is given to the patient by inhalation, the cells in the lungs are expected to produce a functioning CFTR, resulting in normal regulation and production of mucus. This is expected to prevent the lung infections characteristic of cystic fibrosis.

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. Orphan designation of the medicine had been granted in the United States for this condition.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 21 February 2019 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.