Kalydeco (ivacaftor) for cystic fibrosis

Last updated May 7, 2024, by Lindsey Shapiro, PhD
Fact-checked by José Lopes, PhD

What is Kalydeco for CF?

Kalydeco (ivacaftor) is an oral treatment used to improve lung function, reduce the risk of pulmonary exacerbation (acute worsening of symptoms), and lower the levels of sweet chloride in patients with cystic fibrosis (CF) caused by certain mutations. It was the first therapy to address the underlying cause of CF, rather than treating the disease’s symptoms.

Ivacaftor, the active ingredient of Kalydeco, is also a part of:

• Orkambi, a combination therapy that includes lumacaftor
• Symdeko, a combination that includes tezacaftor
• Trikafta, a combination that includes tezacaftor and elexacaftor.

The treatment is marketed by Vertex Pharmaceuticals.

Therapy Snapshot

How does Kalydeco work?

Mutations in the CFTR gene cause CF. The product of this gene is a protein channel that acts as a gate. It can open and close to control the movement of charged salts, such as chloride and sodium, in and out of cells. The level of these salts in the cell influences the movement of water. When the protein channel does not function properly, sticky mucus builds up in various organs.

Different types of CFTR mutations cause CF. A gating mutation results in the production of a faulty CFTR protein that can cause the gate to be stuck closed.

Researchers designed Kalydeco to treat CF patients with gating mutations. It works by keeping the CFTR gate open for longer at the cell surface. This eases the transport of salts and water in and out of cells to improve hydration and clear mucus. In other words, it acts to enhance the activity of the CFTR protein.

The treatment does not increase the amount of CFTR protein produced by cells. This means that it is ineffective for the most common form of CF, which is caused by a mutation known as F508del and results in cells producing little or no CFTR protein.

Who can use Kalydeco?

The U.S. Food and Drug Administration (FDA) initially approved Kalydeco in January 2012 to treat CF patients, 6 and older, with at least one copy of the G551D mutation in the CFTR gene.

The FDA subsequently expanded that approval multiple times. One of those times was in 2018, when Kalydeco was approved to treat CF patients, ages 12 to 24 months. The use of Kalydeco was expanded in 2019 to include children from 6 months of age and in 2020 for infants as young as 4 months with CF caused by one of 97 genetic mutations. Most recently, Kalydeco was approved as a treatment for children from 1 month of age. This approval makes Kalydeco the first medication in its class to be approved for such a young age group.

In Europe, the therapy was approved in 2018 to treat CF patients from 1 year of age, after having been approved for patients aged 2 years and older. In December 2019, the approval included children as young as 6 months and weighing at least 5 kg (about 11 pounds). Kalydeco has also been approved for children 6 months and older who weigh at least 5 kg and carry one of the following CFTR gene mutations: GG551D, G1244E, G1349, G178R, G551S, S1251N, S1255P, S549N, S549R or R117H. The European Commission also extended the approval of Kalydeco for use in infants as young as 1 month.

In Canada, it’s approved to treat CF patients 2 months and older with one of the above mutations and weighing at least 3 kg.

Kalydeco is available in more than 40 countries, though ages and mutations may vary country-by-country.

Who should not use Kalydeco?

There are currently no contraindications for Kalydeco. However, the therapy’s FDA label warns the therapy is not recommended for patients being treated with antibiotics such as rifampin and rifabutin, seizure treatments, antifungal medications, and the herbal therapy St. John’s wort.

Kalydeco has not been approved for children younger than 4 months old.

How is Kalydeco administered?

In the U.S., Kalydeco is available as 150 mg oral tablets, and in 25, 50, and 75 mg oral granule packets.

Each box of oral tablets contain four blister cards, each containing 14 pills (seven morning doses and seven evening doses). Each box of oral granules contains four wallet cards, each containing 14 doses (enough for a week). The dosage depends on patients’ age and weight, as follows:

• 5.8 mg packets, for children 1 month to less than 2 months, weighing 3 kg or more (6.6 lbs or more)
• 13.4 mg packets, for children 2 months to less than 4 months, weighing 3 kg or more (6.6 lbs or more)
• 25 mg packets, for children 4 months to less than 6 months, weighing 5 kg or more (11 lbs or more)
• 25 mg packets, for children 6 months to less than age 6, weighing 5 to less than 7 kg (11 to 15.4 lbs)
• 50 mg packets, for children 6 months to less than age 6, weighing 7 to less than 14 kg (15.4 to less than 30.9 lbs)
• 75 mg packets, for children 6 months to less than age 6, weighing 14 kg or more (30.9 lbs or more)
• 150 mg tablets, for patients ages 6 and older.

Tablets or granule packets should be taken orally every 12 hours. Kalydeco should be taken with fat-containing food. Granule packets dosages should be mixed with one soft food or liquid, such as milk, breast milk or infant formula, puréed fruits or vegetables, yogurt, applesauce, water, and juice. Food and liquids should be stored at or below room temperature. Patients should take the entire mixture.

Grapefruit-containing food should be avoided, as it may affect the amount of the treatment in the body.

Kalydeco in clinical trials

The approval of Kalydeco was based on the results of two Phase 3 clinical trials: STRIVE (NCT00909532) and ENVISION (NCT00909727). In both trials, researchers treated patients with 150 mg of Kalydeco or a placebo, twice a day, together with their usual therapies. The main goal was the improvement in lung function as measured by FEV1 (the amount of air a person can forcibly exhale in one second) through 24 weeks. Secondary assessments included sustained improvement through 48 weeks of follow-up, the respiratory domain of the CF Questionnaire-Revised (CFQ-R) score, the time to first pulmonary exacerbation, and levels of sweat chloride.

STRIVE trial

This 48-week trial enrolled 161 CF patients ages 12 and older with a G551D mutation. Results showed significant improvements in FEV1 by 10.6 points (through 24 weeks) and 10.5 points through 48 weeks. Improvements in CFQ-R were also observed at 24 weeks (8.1 points) and 48 weeks (8.6 points). Patients treated with Kalydeco also reduced their risk of pulmonary exacerbation by 60% at week 24, and 54% at week 48, when compared to placebo. A decrease in sweat chloride levels were also observed.

ENVISION trial

ENVISION also was a 48-week trial that involved 52 CF patients ages 6 to 11 years with a G551D mutation. The study found a 12.5-improvement in FEV1 after 24 weeks and by 10 points at week 48. CFQ-R also was higher, by 6.1 points at week 24 and 5.1 at week 48. Levels of sweet chloride were also lowered.

EXPAND trial

The Phase 3 EXPAND study (NCT02392234) evaluated the effectiveness and safety of the tezacaftor/Kalydeco combination, but also the effects of Kalydeco as a single therapy, in people with a mutation that results in residual CFTR function, and an F508del mutation.

Patients were randomly assigned to take tezacaftor/Kalydeco, Kalydeco monotherapy, or placebo for eight weeks. After that, they underwent an eight-week washout period and switched to one of the other two therapy regimens for more eight weeks. Tezacaftor was given at 100 mg once a day in combination with 150 mg of Kalydeco every 12 hours, while the monotherapy group received Kalydeco 150 mg every 12 hours.

A significant improvement in FEV1 from baseline was observed in both treatments when compared to placebo: an improvement by 6.8 percentage points in patients treated with the combination therapy, and 4.7 percentage points in those treated with Kalydeco alone.

ARRIVAL trial

The ARRIVAL Phase 3 clinical trial (NCT02725567) was launched in 2016 to test the treatment’s safety, pharmacokinetics (movement into, through, and out of the body), and pharmacodynamics (effect on the body). It enrolled 56 children younger than 2 years of age with CF and with a CFTR mutation responsive to Kalydeco. It ran in multiple locations in the U.S., Australia, Canada, Ireland, and the U.K.

Initial trial results showed that Kalydeco was well tolerated and associated with a quick and sustained reduction in sweat chloride in 19 children, 1 to 2 years of age, who completed six months of treatment. In younger children, ages 4 months to less than 1 year, safety results were again favorable. Sweat chloride levels decreased and pancreatic function improved.

The FDA label extension for infants as young as 1 month was based on a group of patients part of the ARRIVAL trial that showed similar safety results to that observed in older children and adults.

Common side effects of Kalydeco

The most common side effects of Kalydeco include:

• headache
• cold-like symptoms, such as sore throat, nasal or sinus congestion, and runny nose
• abdominal pain
• diarrhea
• rash
• nausea
• dizziness.

Elevated levels of liver enzymes

High levels of liver enzymes in the blood may occur in patients taking Kalydeco, which may suggest liver damage. Blood tests are recommended:

• before starting the treatment
• every three months during the first year of treatment
• yearly, while patients are taking the treatment
• more often, for patients who have a history of high liver enzymes.

Treatment should be interrupted if patients have liver enzymes levels greater than five times the upper limit of normal. Resuming the treatment may be considered if liver enzymes levels return to normal.

The treatment dose should be reduced in patients 6 months and older with mild or severe liver injury.

Eye issues

Cases of cataracts — a problem in the eye lens — have been observed in children treated with ivacaftor-containing therapies, including Kalydeco. Eye assessments at the beginning of the treatment and during follow-up are recommended in children who start this treatment.

Dizziness

Kalydeco may cause dizziness in some patients. As such, they are recommended to avoid driving a car, using machinery, or doing any task that needs them to be alert until they know if this treatment causes them this issue.

Use in pregnancy and breastfeeding

Results from animal studies on Kalydeco did not show a treatment-related side effects on the fetus or offspring development. However, clinical trials in pregnant women are limited. As such, it is not known if this treatment will harm the developing fetus. It’s also unknown if Kalydeco may pass to breast milk. The therapy’s label recommends patients to talk to their healthcare team if they are pregnant or plan to become pregnant, are breastfeeding or plan to do so.

Use with other medications

Use of Kalydeco along with strong CYP3A inducers, such as rifampin and St. John’s wort, is not recommended as these medications may reduce the exposure to Kalydeco, therefore decreasing its therapeutic efficacy. Patients treated with strong or moderate CYP3A inhibitors, such as certain antifungal medications, are recommended to use a lower dose of Kalydeco as its effect may be enhanced by such medications.

Cystic Fibrosis News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.