Kaftrio

The medicine can only be obtained with a prescription. Kaftrio should only be prescribed by a healthcare professional with experience in the treatment of cystic fibrosis.

Kaftrio is available as tablets. Each tablet contains 75 mg ivacaftor, 50 mg tezacaftor and 100 mg elexacaftor. Kaftrio should be taken together with another medicine containing ivacaftor alone. The recommended daily dose is two tablets of Kaftrio in the morning with fat‑containing food and one ivacaftor tablet (150 mg) in the evening, about 12 hours later.

The doses of Kaftrio and ivacaftor may need to be reduced if the patient is also taking a type of medicine called a ‘moderate or strong CYP3A inhibitor’, such as certain antibiotics or medicines for fungal infections. The doctor may need to adjust the dose in patients with reduced liver function.

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

Cystic fibrosis is caused by mutations in the CFTR gene. This gene leads to the production of the CFTR protein, which works on the surface of cells to regulate the production of mucus in the lungs and digestive juices in the gut. The mutations reduce the number of CFTR proteins on the cell surface or affect the way the protein works, resulting in secretions of the cells that make mucus and digestive fluids being too thick and leading to blockages, inflammation, increased risk of lung infections, and poor digestion and growth.

Two of the active substances in Kaftrio, elexacaftor and tezacaftor, increase the number of CFTR proteins on the cell surface and the other, ivacaftor, improves the activity of the defective CFTR protein. These actions combine to make lung mucus and digestive juices less thick, thereby helping to relieve symptoms of the disease.

Kaftrio taken together with ivacaftor was effective at improving lung function in three main studies in patients with cystic fibrosis aged 12 years and above. The main measure of effectiveness was ppFEV1, which is the maximum amount of air a person can breathe out in one second compared with values from an average person with similar characteristics (such as age, height and sex). In these studies, patients started off with average values of 60 to 68% of the values from an average healthy person.

The first study involved 403 patients who have an F508del mutation and another type of mutation known as a ‘minimal function’ mutation. After 24 weeks of treatment, patients who took Kaftrio and ivacaftor had an average increase in ppFEV1 of 13.9 percentage points compared with a reduction of 0.4 percentage points in patients who took placebo (a dummy treatment).

In the second study involving 107 patients with an F508del mutation from both parents, patients who took Kaftrio with ivacaftor had an average increase in ppFEV1 of 10.4 percentage points compared with an increase of 0.4 percentage points in patients who took a combination of ivacaftor and tezacaftor alone.

A third study involved 258 patients with an F508del mutation plus either a gating or residual CFTR activity mutation (two other types of mutations). Patients who took Kaftrio with ivacaftor had an average increase in ppFEV1 of 3.7 percentage points compared with an increase of 0.2 percentage points in patients who took ivacaftor alone or a combination of ivacaftor and tezacaftor.

The most common side effects with Kaftrio (which may affect more than 1 in 10 people) are headache, diarrhoea and upper respiratory tract infection (nose and throat infection). Rashes may occur and sometimes be serious.

For the full list of side effects and restrictions of Kaftrio, see the package leaflet.

Kaftrio is an effective treatment for patients with cystic fibrosis who have two F508del mutations or one F508del and one MF mutation. Both are groups with a high unmet medical need. Patients with one F508del mutation plus other mutations were not covered in the studies, and although the company submitted some data on use in such patients, further data was considered necessary to support authorisation in these groups. In terms of safety, Kaftrio was well tolerated. Therefore, the European Medicines Agency decided that Kaftrio’s benefits are greater than its risks and it can be authorised for use in the EU.

The company that markets Kaftrio will carry out a study on the long-term safety of Kaftrio including in pregnant women.

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

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

Kaftrio received a marketing authorisation valid throughout the EU on 21 August 2020.