Kaftrio
Authorised
This medicine is authorised for use in the European Union
ivacaftor / tezacaftor / elexacaftor
MedicineHumanAuthorised
Overview
Kaftrio is a medicine used to treat patients aged 2 years and above who have cystic fibrosis, an inherited disease that has severe effects on the lungs, the digestive system and other organs.
Cystic fibrosis can be caused by various mutations (changes) in the gene for a protein called ‘cystic fibrosis transmembrane conductance regulator’ (CFTR). People have two copies of this gene, one inherited from each parent and the disease only occurs when there is a mutation in both copies.
Kaftrio is used in combination with ivacaftor in patients whose cystic fibrosis is due to at least one F508del mutation in the CFTR gene.
Cystic fibrosis is rare, and Kaftrio was designated an ‘orphan medicine’ (a medicine used in rare diseases) on 14 December 2018. Further information on the orphan designation can be found here:
https://www.ema.europa.eu/en/medicines/human/orphan-designations/eu3182117
Kaftrio contains the active substances ivacaftor, tezacaftor and elexacaftor.
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 and granules in a sachet, both of which come in two different strengths. The dose and formulation depend on the patient’s age and body weight. Kaftrio should be taken in the morning with fat-containing food. It is used together with another medicine containing ivacaftor alone, which should be taken in the evening, about 12 hours after Kaftrio.
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, as they may affect the way Kaftrio and ivacaftor work in the body 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 mucus and digestive fluids being too thick, which leads 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, while 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 (baseline) with average ppFEV1 values that were only 60 to 68% of the values seen in an average healthy person.
The first study involved 403 patients with 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), who were already receiving ivacaftor (patients with a gating mutation) or ivacaftor and tezacaftor (patients with a residual activity mutation). 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.
Treatment with Kaftrio for 24 weeks has also been shown to produce an average increase in ppFEV1 of 10.2 percentage points in a fourth study involving 66 patients aged 6 to less than 12 years; these patients had an F508del mutation from both parents or an F508del mutation and a ‘minimal function’ mutation. The company also provided evidence to support the use of lower doses in this group, which showed that the medicine was distributed in the body to a similar extent as in older children and adults.
Another study involved 75 children aged 2 to 5 years with an F508del mutation from both parents or an F508del mutation and a ‘minimal function’ mutation. In this study, patients received Kaftrio granules for 24 weeks and the medicine was not compared with other treatments. The results showed that treatment with Kaftrio granules reduced the level of chloride in patients’ sweat. Patients with cystic fibrosis have high levels of chloride in sweat due to the CFTR protein not working properly and a decrease in sweat chloride can indicate that the medicine is having an effect. The reduction in sweat chloride level was similar to that seen in older patients in previous studies.
The effectiveness of Kaftrio in children aged 2 to 5 years was also supported by evidence showing that the medicine behaves in the same way in the body of younger children as in that of older children and adults.
For the full list of side effects and restrictions with Kaftrio, see the package leaflet.
The most common side effects with Kaftrio (which may affect more than 1 in 10 people) include headache, diarrhoea and upper respiratory tract infection (nose and throat infection). Rashes may occur and sometimes be serious.
Kaftrio is an effective treatment for patients with cystic fibrosis who have at least one F508del mutation in the CFTR gene. These patients have a high unmet medical need. 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. It will also carry out a study based on a patient registry to provide data on the long-term effectiveness of Kaftrio in children aged 2 to 5 years who have an F508del mutation from one parent.
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.
Product information
Latest procedure affecting product information: PSUSA/00010868/202304
16/02/2024
This medicine’s product information is available in all official EU languages.
Select 'available languages' to access the language you need.
Product information documents contain:
- summary of product characteristics (annex I);
- manufacturing authorisation holder responsible for batch release (annex IIA);
- conditions of the marketing authorisation (annex IIB);
- labelling (annex IIIA);
- package leaflet (annex IIIB).
Product details
- Name of medicine
- Kaftrio
- Active substance
- ivacaftor
- tezacaftor
- elexacaftor
- International non-proprietary name (INN) or common name
- ivacaftor
- tezacaftor
- elexacaftor
- Therapeutic area (MeSH)
- Cystic Fibrosis
- Anatomical therapeutic chemical (ATC) code
- R07AX32
Pharmacotherapeutic group
Other respiratory system productsTherapeutic indication
Kaftrio is indicated in a combination regimen with ivacaftor for the treatment of cystic fibrosis (CF) in patients aged 6 years and older who have at least one F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.
Kaftrio granules are indicated in a combination regimen with ivacaftor for the treatment of cystic fibrosis (CF) in paediatric patients aged 2 to less than 6 years who have at least one F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.
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