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 age 6 months and older for 9 specific genetic mutations and 18 years and older for 38 mutations. In Europe, the medication is approved by the European Commission (EC) for the same age groups. Kalydeco has also been approved in 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 thick, sticky mucus building up 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 influences the movement of water.

There are many different types of CFTR mutations that cause cystic fibrosis. A gating mutation results 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 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 the disease’s symptoms.

Kalydeco in clinical trials

Kalydeco was initially approved by the FDA in January 2012 to treat cystic fibrosis patients age 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) conducted in 167 patients age 12 and older, and the ENVISION trial (NCT00909727) conducted in 52 patients ages 6-11.

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 2 with one of 10 treatable mutations.

In August 2017, the FDA approved Kalydeco for cystic fibrosis patients age 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 also helped to support the subsequent approval of Symdeko (tezacaftor/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 in patients 18 and over. Vertex is planning additional tests that might add more CFTR mutations to the list.

Kalydeco was also approved for patients as young as 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 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 children ages 12-24 months who completed six months of treatment. Results showed the treatment to be well-tolerated and associated with a quick and significant (almost threefold) reduction in sweat chloride. 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 12-24 months with any of these 10 mutations. The EC followed with the same decision in November 2018.

Further data from the ARRIVAL study lead to the FDA expanding the use of Kalydeco to include children 6 months to a year old, weighing 5 kg or more, in May 2019. This expansion includes all 9 mutations previously approved for children under 18 years old. The EC also expanded the use of Kalydeco to include children as young as 6 months in December 2019.


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.

Ivacaftor, the active ingredient of Kalydeko, is also a part of Orkambi, a combination therapy that also includes 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.


Last updated: Dec. 15, 2019


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