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Active Substance: lumacaftor / ivacaftor
Common Name: lumacaftor / ivacaftor
ATC Code: R07AX30
Marketing Authorisation Holder: Vertex Pharmaceuticals (Europe) Ltd
Active Substance: lumacaftor / ivacaftor
Status: Authorised
Authorisation Date: 2015-11-19
Therapeutic Area: Cystic Fibrosis
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.

What is Orkambi and what is it used for?

Orkambi is a medicine used to treat cystic fibrosis in patients aged 6 years and above. 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 is used in patients 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.

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 confirmed to have the F508del mutation in both copies of the CFTR gene.

Orkambi is available as tablets containing either 200 mg lumacaftor and 125 mg ivacaftor (for adults and children aged 12 years and above) or 100 mg lumacaftor and 125 mg ivacaftor (for children aged 6 to 11 years). 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 in the CFTR gene. This gene makes the CFTR protein, which is involved in regulating the production of mucus and digestive juices. The mutations reduce the number of CFTR protein on the cell surface or affect the way the protein works.

One of the active substances in Orkambi, lumacaftor, increases the number of CFTR protein on the cell surface and the other, ivacaftor, increases the activity of the defective CFTR protein. These actions make mucus and digestive juices 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, and in one study involving 204 children aged from 6 to 11 years. All the patients 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.

In the two studies in patients aged 12 years and above, 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.

In the study in children aged 6 to 11 years, the main measure of effectiveness was a decrease in the lung clearance index (LCI2.5), which indicates an improvement in lung ventilation. After 24 weeks of treatment, patients treated with Orkambi had a decrease in LCI2.5 of 1.01 compared with an increase of 0.08 in patients treated 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?

Orkambi has been shown to improve lung function and lung ventilation in patients with cystic fibrosis aged 6 years and above.

The beneficial effects of Orkambi 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 observed effects were considered clinically relevant for patients with no other alternative options. Orkambi’s side effects mainly affected the gut and breathing and were generally considered mild to moderate and manageable.

The European Medicines Agency decided that Orkambi’s benefits are greater than its risks and recommended that it be approved for use in the EU.

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

The company that markets Orkambi is required to conduct a 5-year study in patients with cystic fibrosis to evaluate the long term effects of the medicine.

Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Orkambi have also been included in the summary of product characteristics and the package leaflet.

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.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.