Kalydeco (Ivacaftor)

Kalydeco (ivacaftor) is a treatment by Vertex Pharmaceuticals to treat cystic fibrosis caused by certain mutations.

The therapy is approved in the U.S. and in Europe for patients, 4 months and older, with one of 97 genetic mutations. In Canada, it’s approved for babies as young as 4 months who have one of nine mutations. Kalydeco is currently available in more than 40 countries, though which ages and mutations may vary country-by-country.

How does Kalydeco work?

Mutations in the CFTR gene cause cystic fibrosis. The product of this gene is a protein channel made up of amino acids. This channel has 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 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 cystic fibrosis. 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 cystic fibrosis patients with this gating mutation. 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 cystic fibrosis, which is caused by a mutation known as F508del and results in cells producing little or no CFTR protein.

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

Kalydeco in clinical trials

The U.S. Food and Drug Administration (FDA) initially approved Kalydeco in January 2012 to treat cystic fibrosis patients, 6 and older, with a single type of gating mutation called G551D. The approval was based on the results of two randomized, double-blind, placebo-controlled 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 results 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.

Five years later, the FDA approved Kalydeco in August 2017 for cystic fibrosis patients, 2 and older, who have one of an additional five mutations in the CFTR gene. Those mutations 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 new approval was based on the results of the Phase 3 EXPAND study (NCT02392234) that used Kalydeco as a monotherapy, which was found to be well-tolerated by participants.

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

Ongoing clinical trials

Researchers are currently investigating Kalydeco in an open-label, Phase 3 clinical trial (NCT02725567), called ARRIVAL, which launched in 2016. The trial is testing the treatment’s safety, pharmacokinetics (movement in the body), and pharmacodynamics (effect on the body) of Kalydeco. It is continuing to enroll up to 40 children (up to 24 months old) with cystic fibrosis and one of 10 CFTR gating mutations. It has sites in multiple locations in the U.S., Australia, Canada, Ireland, and the U.K. Researchers expect to conclude the trial in July 2022.

Initial trial results, published in The Lancet Respiratory Medicine in July 2018, showed that Kalydeco was well-tolerated and associated with a quick and significant (nearly threefold) reduction in sweat chloride in 19 children, 12–24 months old, who completed six months of treatment. No one discontinued treatment because of 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 in August 2018 to treat cystic fibrosis patients, ages 12 to 24 months, who are responsive to Kalydeco, based on clinical and/or lab data. The European Commission followed with the same decision in November 2018.

Further data from the ARRIVAL study led to the FDA expanding the use of Kalydeco in May 2019 to include younger children, 6 months to a year old. This expansion included all nine mutations previously approved for children under age 18. The European Commission followed suit in December 2019 to include children as young as 6 months and weighing at least 5 kg.

Following continuing results from the ARRIVAL study, the FDA approved Kalydeco in September 2020 for use in infants as young as 4 months, which was followed by approval in the EU in November 2020.

Other information

In the U.S. and Europe, Kalydeco is available as 150 mg tablets for patients, 6 and older, and in 25, 50, and 75 mg oral granule packets for younger children. 

Ivacaftor, the active ingredient of Kalydeco, is also a part of Orkambi, a combination therapy that includes lumacaftor; Symdeko, a combination that includes tezacaftor; and Trikafta, a combination that includes tezacaftor and elexacaftor.

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 and the risk of cataracts in children.


Last updated: Aug. 27, 2021


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