Orkambi

lumacaftor / ivacaftor

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This is a summary of the European public assessment report (EPAR) for Orkambi. It explains how the Agency assessed the medicine to recommend its authorisation in the EU and its conditions of use. It is not intended to provide practical advice on how to use Orkambi.

For practical information about using Orkambi, patients should read the package leaflet or contact their doctor or pharmacist.

What is Orkambi and what is it used for?

Orkambi is a medicine used to treat cystic fibrosis in patients aged 12 years and above who have a genetic mutation called the F508del mutation. This mutation affects the gene for a protein called cystic fibrosis transmembrane conductance regulator (CFTR) which is involved in regulating the production of mucus and digestive juices. Orkambi is used in patients who have inherited the mutation from both parents and therefore have the mutation in both copies of the CFTR gene.

Cystic fibrosis is an inherited disease that has severe effects on the lungs and the digestive system. It affects the cells that produce mucus and digestive juices. In cystic fibrosis, the secretions become thick and cause blockage. Build-up of thick and sticky secretions in the lungs causes inflammation and long-term infection. In the gut, blockage of the tubes from the pancreas slows down the digestion of food and causes poor growth.

Orkambi contains the active substances lumacaftor and ivacaftor.

How is Orkambi used?

Orkambi can only be prescribed by a doctor with experience in the treatment of cystic fibrosis. It should be prescribed only to patients aged 12 years and above confirmed to have the F508del mutation in both copies of the CFTR gene.

Orkambi is available as tablets containing 200 mg lumacaftor and 125 mg ivacaftor. The recommended dose of Orkambi is two tablets twice a day, taken 12 hours apart with fat-containing foods, such as meals prepared with butter or oils or foods containing eggs, cheese, nuts, whole milk or meats.

The dose of Orkambi may have to be reduced in patients with liver problems and in patients taking certain medicines called strong CYP3A4 inhibitors.

How does Orkambi work?

Cystic fibrosis is caused by mutations of the CFTR gene. This gene makes a protein called ‘cystic-fibrosis transmembrane conductance regulator’ (CFTR), which is involved in regulating the production of mucus and digestive juices. These mutations reduce the number of CFTR protein channels on the cell surface or affect the way they work. These channels are used for the transport of ions (charged atoms and molecules) in and out of cells. When the channels are defective, mucus and digestive juices can become abnormally thick and sticky.

One of the active substances in Orkambi, lumacaftor, increases the number of CFTR proteins on the cell surface and the other, ivacaftor, increases the activity of the defective CFTR protein. This normalises the transport of ions through channels making the secretions less thick.

What benefits of Orkambi have been shown in studies?

Orkambi was shown to be effective at improving lung function in two main studies involving 1,108 cystic fibrosis patients aged 12 years and above who had the F508del mutation in both copies of the CFTR gene. In the studies, Orkambi was compared with placebo (a dummy treatment), both added to patients’ usual therapy. The main measure of effectiveness was based on improvement in patients’ percent of predicted FEV1 which is a measure of how well the lungs work.

Results from the first study showed that after 24 weeks of treatment patients who took Orkambi had an average improvement in FEV1 of 2.41 percentage points more than those who took placebo, whereas this figure was 2.65 in the second study.

Treatment with Orkambi also led to a reduction in the number of exacerbations (flares-up) requiring hospital admission or antibiotic therapy. Overall the number of exacerbations was reduced by 39% when compared with placebo.

What are the risks associated with Orkambi?

The most common side effects with Orkambi (which may affect more than 1 in 10 people) are dyspnoea (shortness of breath), diarrhoea and nausea (feeling sick). Serious side effects included liver problems such as raised liver enzymes, cholestatic hepatitis (build-up of bile leading to inflammation of the liver) and hepatic encephalopathy (a brain disease caused by liver problems). In total, these serious side effects occurred in more than 1 in 200 people during the clinical studies.

For the full list of all side effects and restrictions with Orkambi, see the package leaflet.

Why is Orkambi approved?

The Agency’s Committee for Medicinal Products for Human Use (CHMP) decided that Orkambi’s benefits are greater than its risks and recommended that it be approved for use in the EU.

Although the beneficial effects of Orkambi were consistent across studies and similar to medicines that treat symptoms of cystic fibrosis they were smaller than expected for a medicine that treats the mechanism of the disease rather than its symptoms. However, as cystic fibrosis caused by F508del mutation is particularly severe the CHMP considered that the observed effects seen were clinically relevant for patients with no other alternative options. In addition the committee noted that the benefits of Orkambi were maintained for the duration of treatment of 48 weeks. Orkambi’s side effects mainly affected the gut and breathing and were generally considered mild to moderate and manageable.

What measures are being taken to ensure the safe and effective use of Orkambi?

A risk management plan has been developed to ensure that Orkambi is used as safely as possible. Based on this plan, safety information has been included in the summary of product characteristics and the package leaflet for Orkambi, including the appropriate precautions to be followed by healthcare professionals and patients.

Further information can be found in the summary of the risk management plan.

Other information about Orkambi

The European Commission granted a marketing authorisation valid throughout the European Union for Orkambi on 19 November 2015.

For more information about treatment with Orkambi, read the package leaflet (also part of the EPAR) or contact your doctor or pharmacist.

Name Language First published Last updated
Orkambi : EPAR - Summary for the public BG = bălgarski 01/12/2015  
Orkambi : EPAR - Summary for the public ES = español 01/12/2015  
Orkambi : EPAR - Summary for the public CS = čeština 01/12/2015  
Orkambi : EPAR - Summary for the public DA = dansk 01/12/2015  
Orkambi : EPAR - Summary for the public DE = Deutsch 01/12/2015  
Orkambi : EPAR - Summary for the public ET = eesti keel 01/12/2015  
Orkambi : EPAR - Summary for the public EL = elliniká 01/12/2015  
Orkambi : EPAR - Summary for the public EN = English 01/12/2015  
Orkambi : EPAR - Summary for the public FR = français 01/12/2015  
Orkambi : EPAR - Summary for the public IT = italiano 01/12/2015  
Orkambi : EPAR - Summary for the public LV = latviešu valoda 01/12/2015  
Orkambi : EPAR - Summary for the public LT = lietuvių kalba 01/12/2015  
Orkambi : EPAR - Summary for the public HU = magyar 01/12/2015  
Orkambi : EPAR - Summary for the public MT = Malti 01/12/2015  
Orkambi : EPAR - Summary for the public NL = Nederlands 01/12/2015  
Orkambi : EPAR - Summary for the public PL = polski 01/12/2015  
Orkambi : EPAR - Summary for the public PT = português 01/12/2015  
Orkambi : EPAR - Summary for the public RO = română 01/12/2015  
Orkambi : EPAR - Summary for the public SK = slovenčina 01/12/2015  
Orkambi : EPAR - Summary for the public SL = slovenščina 01/12/2015  
Orkambi : EPAR - Summary for the public FI = suomi 01/12/2015  
Orkambi : EPAR - Summary for the public SV = svenska 01/12/2015  
Orkambi : EPAR - Summary for the public HR = Hrvatski 01/12/2015  
Name Language First published Last updated
Orkambi : EPAR - Risk-management-plan summary (English only) 01/12/2015  

This EPAR was last updated on 27/05/2016 .

Authorisation details

Product details

Product details for Orkambi
NameOrkambi
Agency product numberEMEA/H/C/003954
Active substance

lumacaftor / ivacaftor

International non-proprietary name (INN) or common name

lumacaftor / ivacaftor

Therapeutic area Cystic Fibrosis
Anatomical therapeutic chemical (ATC) code R07AX30
Additional monitoring

This medicine is under additional monitoring. This means that it is being monitored even more intensively than other medicines. For more information, see medicines under additional monitoring.

Publication details

Publication details for Orkambi
Marketing-authorisation holder

Vertex Pharmaceuticals (Europe) Ltd

Revision2
Date of issue of marketing authorisation valid throughout the European Union19/11/2015

Contact address:

Vertex Pharmaceuticals (Europe) Ltd
2 Kingdom Street
London W2 6BD
United Kingdom

Product information

Product information

28/04/2016  Orkambi -EMEA/H/C/003954 -II/0002

Name Language First published Last updated
Orkambi : EPAR - Product Information EN = English 01/12/2015 27/05/2016
Orkambi : EPAR - Product Information EN = English 01/12/2015 27/05/2016
Orkambi : EPAR - Product Information EN = English 01/12/2015 27/05/2016
Orkambi : EPAR - Product Information EN = English 01/12/2015 27/05/2016
Orkambi : EPAR - Product Information EN = English 01/12/2015 27/05/2016
Orkambi : EPAR - Product Information EN = English 01/12/2015 27/05/2016
Orkambi : EPAR - Product Information EN = English 01/12/2015 27/05/2016
Orkambi : EPAR - Product Information EN = English 01/12/2015 27/05/2016
Orkambi : EPAR - Product Information EN = English 01/12/2015 27/05/2016
Orkambi : EPAR - Product Information EN = English 01/12/2015 27/05/2016
Orkambi : EPAR - Product Information EN = English 01/12/2015 27/05/2016
Orkambi : EPAR - Product Information EN = English 01/12/2015 27/05/2016
Orkambi : EPAR - Product Information EN = English 01/12/2015 27/05/2016
Orkambi : EPAR - Product Information EN = English 01/12/2015 27/05/2016
Orkambi : EPAR - Product Information EN = English 01/12/2015 27/05/2016
Orkambi : EPAR - Product Information EN = English 01/12/2015 27/05/2016
Orkambi : EPAR - Product Information EN = English 01/12/2015 27/05/2016
Orkambi : EPAR - Product Information EN = English 01/12/2015 27/05/2016
Orkambi : EPAR - Product Information EN = English 01/12/2015 27/05/2016
Orkambi : EPAR - Product Information EN = English 01/12/2015 27/05/2016
Orkambi : EPAR - Product Information EN = English 01/12/2015 27/05/2016
Orkambi : EPAR - Product Information EN = English 01/12/2015 27/05/2016
Orkambi : EPAR - Product Information EN = English 01/12/2015 27/05/2016
Orkambi : EPAR - Product Information EN = English 01/12/2015 27/05/2016
Orkambi : EPAR - Product Information EN = English 01/12/2015 27/05/2016

Contents

  • Annex I - Summary of product characteristics
  • Annex IIA - Manufacturing-authorisation holder responsible for batch release
  • Annex IIB - Conditions of the marketing authorisation
  • Annex IIIA - Labelling
  • Annex IIIB - Package leaflet

Please note that the size of the above document can exceed 50 pages.

You are therefore advised to be selective about which sections or pages you wish to print.


Name Language First published Last updated
Orkambi : EPAR - All Authorised presentations EN = English 01/12/2015 15/03/2016
Orkambi : EPAR - All Authorised presentations EN = English 01/12/2015 15/03/2016
Orkambi : EPAR - All Authorised presentations EN = English 01/12/2015 15/03/2016
Orkambi : EPAR - All Authorised presentations EN = English 01/12/2015 15/03/2016
Orkambi : EPAR - All Authorised presentations EN = English 01/12/2015 15/03/2016
Orkambi : EPAR - All Authorised presentations EN = English 01/12/2015 15/03/2016
Orkambi : EPAR - All Authorised presentations EN = English 01/12/2015 15/03/2016
Orkambi : EPAR - All Authorised presentations EN = English 01/12/2015 15/03/2016
Orkambi : EPAR - All Authorised presentations EN = English 01/12/2015 15/03/2016
Orkambi : EPAR - All Authorised presentations EN = English 01/12/2015 15/03/2016
Orkambi : EPAR - All Authorised presentations EN = English 01/12/2015 15/03/2016
Orkambi : EPAR - All Authorised presentations EN = English 01/12/2015 15/03/2016
Orkambi : EPAR - All Authorised presentations EN = English 01/12/2015 15/03/2016
Orkambi : EPAR - All Authorised presentations EN = English 01/12/2015 15/03/2016
Orkambi : EPAR - All Authorised presentations EN = English 01/12/2015 15/03/2016
Orkambi : EPAR - All Authorised presentations EN = English 01/12/2015 15/03/2016
Orkambi : EPAR - All Authorised presentations EN = English 01/12/2015 15/03/2016
Orkambi : EPAR - All Authorised presentations EN = English 01/12/2015 15/03/2016
Orkambi : EPAR - All Authorised presentations EN = English 01/12/2015 15/03/2016
Orkambi : EPAR - All Authorised presentations EN = English 01/12/2015 15/03/2016
Orkambi : EPAR - All Authorised presentations EN = English 01/12/2015 15/03/2016
Orkambi : EPAR - All Authorised presentations EN = English 01/12/2015 15/03/2016
Orkambi : EPAR - All Authorised presentations EN = English 01/12/2015 15/03/2016
Orkambi : EPAR - All Authorised presentations EN = English 01/12/2015 15/03/2016
Orkambi : EPAR - All Authorised presentations EN = English 01/12/2015 15/03/2016

Pharmacotherapeutic group

Other respiratory system products

Therapeutic indication

Orkambi is indicated for the treatment of cystic fibrosis (CF) in patients aged 12 years and older who are homozygous for the F508del mutation in the CFTR gene.

Assessment History

Changes since initial authorisation of medicine

Name Language First published Last updated
Orkambi : EPAR - Procedural steps taken and scientific information after authorisation EN = English 15/03/2016 27/05/2016

Initial marketing-authorisation documents

Name Language First published Last updated
Orkambi : EPAR - Public assessment report EN = English 01/12/2015  
CHMP summary of positive opinion Orkambi EN = English 25/09/2015  

Authorised

This medicine is approved for use in the European Union

More information on Orkambi

This product is no longer an orphan medicine. It was originally designated an orphan medicine on 20 September 2010. Upon request of the marketing-authorisation holder, Orkambi has now been removed from the Community register of orphan medicinal products.