Kalydeco (ivacaftor) is a treatment developed and marketed by Vertex Pharmaceuticals for the treatment of cystic fibrosis (CF) caused by particular mutations. The treatment is approved by the U.S. Food and Drug Administration (FDA) for patients ages 2 and older. It has also been approved in Europe, Canada, Australia, and New Zealand.

How Kalydeco works

Cystic fibrosis is a genetic condition caused by a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which results in a thick sticky mucus building up in various organs. CFTR is a protein channel produced 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 mutation that cause CF. “Gating” mutations result in the production of a faulty CFTR protein,  where the gate can be stuck closed.

Kalydeco is designed to treat this particular type of mutation. It works to keep the CFTR gate open longer at the cell surface to ease the transport of salt and water through cells, improving hydration and mucus clearance. In other words, it acts to enhance the activity of the CFTR protein. It does not increase the amount of CFTR produced and so is ineffective in the most common form of CF (F508del), which results in little or no CFTR being produced.

Kalydeco is the first therapy to address the underlying cause of CF instead of treating only its symptoms.

Kalydeco in clinical trials

Kalydeco was initially approved by the FDA in January 2012 to treat CF patients ages 6 and older with a single type of gating mutation (called G551D). The approval was based on two randomized, double-blind, placebo-controlled clinical trials. These were 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 prescribed CF 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 were persistent through 48 weeks of follow-up.

In March 2015, the FDA approved Kalydeco to be given to CF patients as young as 2 years old with one of the approved mutations.

Vertex continued testing the effect of Kalydeco in different CF mutations through multiple clinical trials, resulting in the indication for the drug being significantly expanded over the years to treat individuals with 38 different gating mutations.

In August 2017, the FDA approved Kalydeco for use in CF patients ages 2 and older who have one of an additional five mutations in the CFTR gene that result in a splicing defect in the CFTR gene, 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 as a monotherapy 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 who have one mutation that results in residual CFTR function and one F508del mutation. The study met its primary endpoints, with improvements in lung function with the combination treatment as well as Kalydeco monotherapy.   

The treatment may now be prescribed to more than 600 additional people with CF in the U.S. having one of these five mutations, and the total number of CFTR mutations treatable by Kalydeco is 38. The manufacturers are planning tests that might add more CFTR mutations to the list of mutations treatable with Kalydeco.

Kalydeco is currently being studied in a Phase 3 clinical trial (NCT02725567) in about 35 children with CF under age 2 (newborns to toddlers) with one of nine CFTR mutations. The trial is testing the safety, pharmacokinetics (movement in the body), and pharmacodynamics (effect on the body) of the treatment. The two-part, open-label study is currently recruiting participants across the U.S., Canada, and Australia, and is expected to be completed in June 2020.

Other information

In Canada, where the minimum age to use Kalydeco is 6, the drug is available in 150 mg tablets. In the U.S. and Europe, additional 50 mg and 75 mg oral granules are available for patients ages 2 to 6, based on weight. Treatment with Kalydeco is not effective in CF patients who have two copies of the F508del mutation in the CFTR gene. The treatment’s use in infants and toddlers under age 2 is not approved, but is under study.

Headaches, upper respiratory tract infections, stomach pain, and diarrhea are some of the common side effects of Kalydeco. The drug’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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