Kalydeco (ivacaftor) is a treatment developed and marketed by Vertex Pharmaceuticals to treat cystic fibrosis that is caused by certain mutations. The treatment is approved by the U.S. Food and Drug Administration (FDA) for patients, ages 12 months and older. Kalydeco has also been approved in Europe, Canada, Australia, and New Zealand.

How Kalydeco works

Cystic fibrosis is a genetic condition caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which results in a thick sticky mucus building in various organs. The product of the CFTR gene is a protein channel made by mucus-producing cells, with a “gate” that can open and close to control the movement of charged salts, such as chloride and sodium, in and out of cells. The level of salts in the cell influence the movement of water.

There are many different types of CFTR mutations that cause cystic fibrosis. Gating mutations is the name given to gene variants that result in the production of a faulty CFTR protein which can cause the “gate” to be stuck closed.

Kalydeco is designed to treat cystic fibrosis patients with this particular type of mutation. It works by keeping the CFTR gate open for longer at the cell surface, easing the transport of salts and water in and out of cells to improve hydration and mucus clearance. In other words, it acts to enhance the activity of the CFTR protein.

Kalydeco does not increase the amount of CFTR protein produced, making it ineffective for the most common form of cystic fibrosis, which is caused by a mutation known as F508del and results in little or no CFTR protein being produced.

Kalydeco was the first therapy to address the underlying cause of cystic fibrosis, rather than treating only the disease’s symptoms.

Kalydeco in clinical trials

Kalydeco was initially approved by the FDA in January 2012 to treat cystic fibrosis patients, ages 6 and older, with a single type of gating mutation called G551D. This approval was based on two randomized, double-blind, placebo-controlled clinical trials — the STRIVE trial (NCT00909532) in 167 patients ages 12 and older, and the ENVISION trial (NCT00909727) in 52 patients ages 6 to 11.

In both trials, patients were treated with 150 mg of Kalydeco or a placebo twice a day, together with their prescribed cystic fibrosis therapies. The trials supported Kalydeco’s safety and superiority in improving lung function as measured by FEV1 (the amount of air a person can forcibly exhale in one second). Improvements persisted through 48 weeks of follow-up.

In March 2015, the FDA approved Kalydeco for cystic fibrosis patients as young as age 2 with one of 10 treatable mutations.

In August 2017, the FDA approved Kalydeco for cystic fibrosis patients, ages 2 and older, who have one of an additional five mutations in the CFTR gene that result in a splicing defect, causing a moderate loss of chloride transport. Patients with these mutations experience a progressive decline in lung function and other complications. 

This approval was based on the results of the Phase 3 EXPAND study (NCT02392234), in which Kalydeco was used as a monotherapy and was generally well-tolerated. EXPAND was an eight-week crossover study that also evaluated the effect of a combination therapy of Kalydeco with tezacaftor in people with a mutation that results in residual CFTR function and an F508del mutation. The study met its primary objectives, with improvements in lung function in patients receiving the combination treatment as well as Kalydeco monotherapy.  [This trial helped to support subsequent approval of Symdeko (tezacaftor/ivacaftor and ivacaftor).] 

Kalydeco may now be prescribed to more than 600 additional people with cystic fibrosis in the U.S. who have one of these five mutations, bringing the total number of CFTR mutations Kalydeco can treat to 38. Vertex is planning additional tests that might add more CFTR mutations to this list.

Kalydeco is also approved for patients starting at 12 months old. This decision followed early results of an open-label Phase 3 clinical trial (NCT02725567), called ARRIVAL, in up to 35 infants and toddlers (newborns to 24 months old) with cystic fibrosis younger and one of 10 CFTR gating mutations. The trial is testing the treatment’s safety, pharmacokinetics (movement in the body), and pharmacodynamics (effect on the body), and is expected to conclude in June 2020.

Initial results from the ARRIVAL study were published in The Lancet Respiratory Medicine, looking at 19 toddlers (12 to 24 months old) who completed six months of treatment. Results showed the treatment to be well-tolerated and associated with a quick and significant (almost three-fold) reduction in sweat chloride. No one discontinued treatment due to safety concerns. The most common side effects included coughing, fever, increased liver enzyme levels, and a runny nose. Based on these results, the FDA approved Kalydeco to treat pediatric CF patients 12 to 24 months old with any of these 10 mutations in August 2018.

Other information

In Canada, where the minimum approved age for Kalydeco use is 6, the treatment is available in 150 mg tablets. In the U.S. and Europe, Kayldeco is also available as 50 mg and 75 mg oral granules for patients up to age 6, according to their weight. Treatment with Kalydeco is not effective in cystic fibrosis patients who have two copies of the F508del mutation in the CFTR gene.

The treatment’s use in infants under age of one is not approved. However, this age group is being investigated in the ARRIVAL study.

Ivacaftor is a part of Orkambi, a combination therapy with lumacaftor.

Headaches, upper respiratory tract infections, stomach pain, and diarrhea are some of the common side effects of Kalydeco. The medication’s label warns about the risk of elevated levels of liver enzymes, called transaminases, as well as cataracts in children.


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.

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