Orkambi

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 and granules. The recommended dose depends on the age and weight of the patient. The tablets or granules are taken every 12 hours with fat-containing foods.

For more information about using Orkambi, see the package leaflet or contact your doctor or pharmacist.

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 amount of CFTR protein on the cell surface or affect the way the protein works.

One of the active substances in Orkambi, lumacaftor, increases the amount of CFTR protein on the cell and the other, ivacaftor, increases the activity of the defective CFTR protein. These actions make mucus and digestive juices less thick.

Orkambi improved lung function in two main studies involving 1,108 cystic fibrosis patients aged 12 years and above, and one study involving 204 children aged from 6 to 11 years. All patients had the F508del mutation in 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’ 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; this figure was 2.65 in the second study. Treatment with Orkambi also reduced 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 (LCI_2.5), which indicates an improvement in lung ventilation. After 24 weeks of treatment, LCI_2.5 decreased by 1.01 in patients treated with Orkambi compared with an increase of 0.08 in patients treated with placebo.

A further study involved 60 children aged 2 to 5 years with cystic fibrosis who had the F508del mutation in the CFTR gene. All children were treated with Orkambi. There was improvement in CFTR protein activity as measured by a decrease in the amount of chloride in sweat after 24 weeks of treatment. Patients with cystic fibrosis have high levels of chloride in sweat due to CFTR not working properly. Stopping treatment with Orkambi caused chloride levels to rise again. The children's growth (measured in terms of the body mass index, weight and height) also improved.

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 include 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.

Orkambi has been shown to improve lung function and lung ventilation in patients with cystic fibrosis from 6 years of age. The effects of Orkambi in children aged 2 to 5 years were considered to be similar to those in older children and a long-term study will be carried out to confirm this.

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 option. 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.

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. A further long-term study in children aged 2 to 5 years with cystic fibrosis is also required to compare those who have the F508del mutation in the CFTR gene and are treated with Orkambi with those who have not been treated with Orkambi. The study is to evaluate how the disease progresses in the two groups of children.

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.

As for all medicines, data on the use of Orkambi are continuously monitored. Side effects reported with Orkambi are carefully evaluated and any necessary action taken to protect patients.

Orkambi received a marketing authorisation valid throughout the EU on 19 November 2015.