Kalydeco

Kalydeco can only be obtained with a prescription. It should only be prescribed by a doctor with experience in the treatment of cystic fibrosis, and only in patients confirmed to have the mutations mentioned above.

Kalydeco is available as tablets and as granules in a sachet. For infants and children aged 4 months and above and weighing 5 to 25 kg, the granules should be used. They should be mixed with 5 ml of soft food or liquid to make a suspension to be taken by mouth.

The tablets are used in adults and children aged 6 years and above and weighing 25 kg or more.

The dose and frequency depend on whether Kalydeco is used alone or together with tezacaftor plus ivacaftor or together with ivacaftor, tezacaftor and elexacaftor.

The dose of Kalydeco may need to be adjusted 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, and these medicines should not be taken with Kalydeco by patients aged 4–6 months. The dose may also need to be adjusted in patients with reduced liver function.

For more information about using Kalydeco, 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 works on the surface of cells to regulate the production of mucus and digestive juices. The mutations reduce the number of CFTR proteins on the cell surface or affect the way the protein works.

The active substance in Kalydeco, ivacaftor, increases the activity of the defective CFTR protein. This makes mucus and digestive juices less thick, thereby helping to relieve symptoms of the disease.

G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N, S549R, R117H mutations

Kalydeco was shown to be effective at improving lung function in 4 main studies involving patients with cystic fibrosis who had various mutations. The main measure of effectiveness in these studies was based on improvements in patients’ FEV1. FEV1 is the maximum amount of air a person can breathe out in one second and is a measure of how well the lungs work. In the studies, Kalydeco was compared with placebo (a dummy treatment).

Two of the studies involved 219 patients with cystic fibrosis who had the G551D mutation. One of the studies was in patients aged over 12 years, while the other was in patients aged between 6 and 11 years. After 24 weeks of treatment, patients aged 12 years and older who took Kalydeco had an average improvement in FEV1 of 10.6 percentage points more than those who took placebo. Similar results were seen in patients aged between 6 and 11 years, where Kalydeco treatment led to an improvement of 12.5 percentage points more than treatment with placebo.

The third study involved 39 patients over 6 years of age with cystic fibrosis due to several mutations other than G551D. After 8 weeks of treatment, patients who took Kalydeco had an average improvement in FEV1 of 10.7 percentage points more than those who took placebo.

The fourth study involved 69 patients aged 6 years and above with cystic fibrosis who had the R117H mutation. When analysing the subset of patients aged 18 years and above alone, an average improvement in FEV1 of around 5 percentage points was seen in patients who took Kalydeco compared with patients who took placebo. However, no difference was seen between placebo and Kalydeco for children aged 6 years and above. The study also looked at changes in the level of chloride in patients’ sweat. In all age groups, patients who took Kalydeco had a decrease in sweat chloride level compared with those who took placebo. Patients with cystic fibrosis have high levels of chloride in sweat due to CFTR not working properly and a decrease in sweat chloride can indicate that the medicine is having an effect.

Another study investigated Kalydeco granules in 34 patients aged between 2 and 5 years of age who had cystic fibrosis due to a G551D or S549N mutation. The study found that Kalydeco granules resulted in increased bodyweight and a decrease in sweat chloride. Patients with cystic fibrosis have low bodyweight due to problems with digestion of food.

Positive results were also shown with Kalydeco granules in a study involving 6 children aged 4 months to less than 6 months, 11 children aged 6 months to less than 12 months and 19 children aged 12 months to less than 24 months.

F508del mutation from both parents or F508del mutation from one parent and one of the following mutations from the second parent: P67L, R117C, L206W, R352Q, A455E, D579G, 711+3A→G, S945L, S977F, R1070W, D1152H, 2789+5G→A, 3272 26A→G or 3849+10kbC→T

Kalydeco taken together with tezacaftor plus ivacaftor was shown to be effective at improving lung function in two main studies of patients with cystic fibrosis aged 12 years and above and one study of patients from 6 up to 12 years.

The first study involved 510 patients with cystic fibrosis who inherited the F508del mutation from both parents. Kalydeco taken with tezacaftor plus ivacaftor was compared with placebo. After 24 weeks of treatment, patients who took the medicines had an average increase in FEV1 of 3.4 percentage points compared with a reduction of 0.6 percentage points in patients who took placebo.

The second study involved 248 patients with cystic fibrosis who inherited the F508del mutation from one parent and who also have another CFTR mutation. Kalydeco taken with tezacaftor plus ivacaftor was compared with Kalydeco taken alone and with placebo. Lung function was measured after 4 and 8 weeks of treatment. Patients who took Kalydeco and tezacaftor plus ivacaftor had an average increase in FEV1 of 6.5 percentage points compared with an increase of 4.4 percentage points in patients who took Kalydeco alone and a reduction of 0.3 percentage points in patients who took placebo.

The study of patients aged from 6 up to 12 years involved 69 patients who had the F508del mutation from both parents or from one parent together with another mutation. The study looked at a measure of lung disease called the lung clearance index (LCI). After 8 weeks of treatment, patients who took Kalydeco together with tezacaftor plus ivacaftor had a moderate decrease in LCI, which can indicate that the medicine is having an effect.

F508del mutation from both parents or F508del mutation from one parent

Kalydeco taken together with ivacaftor, tezacaftor and elexacaftor was effective at improving lung function in four main studies in patients with cystic fibrosis aged 6 years and above. The main measure of effectiveness was ppFEV1, which is a person’s FEV1 compared with that of an average person with similar characteristics (such as age, height and sex). In these studies, patients started off with average values of 60 to 88.8% of the values for an average healthy person.

The first study involved 403 patients aged 12 years and older who have an F508del mutation and another type of mutation known as a ‘minimal function’ mutation. After 24 weeks of treatment, patients who took Kalydeco and ivacaftor, tezacaftor plus elexacaftor 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.

In the second study involving 107 patients aged 12 years and older with an F508del mutation from both parents, patients who took Kalydeco and ivacaftor, tezacaftor plus elexacaftor 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 Kalydeco and tezacaftor.

A third study involved 258 patients aged 12 years and older with an F508del mutation plus either a gating or residual CFTR activity mutation (two other types of mutations). Patients who took Kalydeco with ivacaftor, tezacaftor and elexacaftor had an average increase in ppFEV1 of 3.7 percentage points compared with an increase of 0.2 percentage points in patients who took Kalydeco alone or a combination of Kalydeco and tezacaftor.

The last study involved 66 children aged 6 to 11 years with either an F508del mutation from both parents or an F508del mutation and a ‘minimal function’ mutation. Kalydeco with ivacaftor, tezacaftor, and elexacaftor was not compared with other treatments. Patients had an increase in ppFEV1 and a decrease in sweat chloride levels, similar to previous observations in adults and adolescents taking Kalydeco with ivacaftor, tezacaftor and elexacaftor.

The most common side effects with Kalydeco (which may affect more than 1 in 10 people) are headache, sore throat, upper respiratory tract infection (nose and throat infection), nasal congestion (blocked nose), abdominal (belly) pain, nasopharyngitis (inflammation of the nose and throat), diarrhoea, dizziness, rash, bacteria in sputum (phlegm) and an increase in certain liver enzymes. Serious side effects include increased liver enzymes, which can indicate liver damage, and abdominal pain.

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

Kalydeco used on its own or together with tezacaftor plus ivacaftor or with ivacaftor, tezacaftor and elexacaftor has been shown to improve lung function or sweat chloride levels in patients with specific mutations. The medicine has an acceptable safety profile. The European Medicines Agency therefore decided that the benefits of Kalydeco are greater than its risks and it can be authorised for use in the EU. The Agency also noted, however, that there were limited data on the longer-term effects of the medicine and that further data should be provided by the company.

The company that markets Kalydeco is conducting a study in children aged 2 to 5 years starting treatment to assess long-term effects of early treatment.

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

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

Kalydeco received a marketing authorisation valid throughout the EU on 23 July 2012.