EU/3/14/1333 - orphan designation for treatment of cystic fibrosis

Lumacaftor

ivacaftor

Overview

Please note that this product (marketed as Orkambi) was withdrawn from the Community Register of designated orphan medicinal products in October 2015 upon request of the marketing authorisation holder at the time of the granting of a marketing authorisation.

On 22 August 2014, orphan designation (EU/3/14/1333) was granted by the European Commission to Vertex Pharmaceuticals (U.K.) Limited, United Kingdom, for lumacaftor/ivacaftor 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 0.8 in 10,000 people in the European Union (EU). This was equivalent to a total of around 41,000 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 treat a subgroup of patients with cystic fibrosis who have a specific mutation (defect) called 'G551D' in the gene for CFTR. 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. Regular exercise and physiotherapy were also part of the treatment.

The sponsor has provided sufficient information to show that lumacaftor/ivacaftor might be of significant benefit for patients with cystic fibrosis because early studies showed an improvement in patients' lung function when used together with current treatments. 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 is a fixed-dose combination of ivacaftor and lumacaftor. Both ivacaftor and lumacaftor are expected to act on the defective CFTR in cystic fibrosis patients.

Ivafactor works by increasing the activity of the defective CFTR while lumacaftor is thought to help produce some amount of functional CFTR protein. These actions are expected to normalise the transport of ions in and out of cells making the secretions less think and thereby relieving the symptoms of the disease.

What is the stage of development of this medicine?

The effects of lumacaftor/ivacaftor have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with lumacaftor/ivacaftor in patients with cystic fibrosis were ongoing.

At the time of submission, lumacaftor/ivacaftor was not authorised anywhere in the EU for cystic fibrosis or designated as an orphan medicinal product elsewhere for this condition. The single components lumacaftor and ivacaftor both have orphan designations in the EU for cystic fibrosis.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 10 July 2014 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/3/14/1333: Public summary of opinion on orphan designation: Lumacaftor/ivacaftor for the treatment of cystic fibrosis

AdoptedReference Number: EMA/COMP/440253/2014

Key facts

• Active substance:
  • Lumacaftor
  • ivacaftor
• Medicine name:
  Orkambi
• Intended use:
  Treatment of cystic fibrosis
• Orphan designation status:
  Withdrawn
• EU designation number:
  EU/3/14/1333
• Date of designation:
  22/08/2014
• Sponsor:

  Vertex Pharmaceuticals (U.K.) Limited; Cardinal Point; Park Road; Rickmansworth; Hertfordshire WD3 1RE; United Kingdom; Tel. [phone]; Fax [phone]; E-mail: [e-mail]

Review of designation

Please note that this product (marketed as Orkambi) was withdrawn from the Community Register of designated orphan medicinal products in October 2015 upon request of the marketing authorisation holder at the time of the granting of a marketing authorisation.