Kalydeco (ivacaftor) is a treatment developed and marketed by Vertex Pharmaceuticals for the treatment of cystic fibrosis caused by certain mutations. The treatment is approved by the U.S. Food and Drug Administration 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. The product of the CFTR gene 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 mutations that cause cystic fibrosis. “Gating” mutations result in the production of a faulty CFTR protein, where the gate can be stuck closed.

Kalydeco is designed to treat cystic fibrosis caused by 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 protein produced, making it ineffective for the most common form of cystic fibrosis caused by a mutation known as F508del, which results in little or no production of the CFTR protein.

Kalydeco is the first therapy to address the underlying cause of cystic fibrosis rather than treating only the 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). The approval was based on two randomized, double-blind, placebo-controlled clinical trials — the STRIVE trial (NCT00909532), conducted in 167 patients, ages 12 and older, and the ENVISION trial (NCT00909727), conducted 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 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 the approved mutations.

Vertex continued testing the effect of Kalydeco in different cystic fibrosis-causing mutations through multiple clinical trials, resulting in the indication for the treatment being significantly expanded over the years.

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 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 objectives, 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 cystic fibrosis in the U.S. who have one of these five mutations, bringing the total number of CFTR mutations treatable by Kalydeco to 38. The manufacturers are planning additional tests that might add more CFTR mutations to this list.

Kalydeco is currently being studied in an ongoing Phase 3 clinical trial (NCT02725567) called ARRIVAL in roughly 35 children with cystic fibrosis younger than 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, U.K, Ireland, and Australia, and is expected to be completed in June 2020.

Initial results from ARRIVAL have been published in The Lancet Respiratory Medicine, which included 19 children, ages 12 to 24 months, who completed the trial. The treatment was well-tolerated and associated with a quick and significant reduction in sweat chloride. None of the children discontinued treatment due to safety concerns, and the most common side effects included coughing, fever, increased liver enzyme levels, and a runny nose. Based on these results, on Aug. 15, 2018, the FDA approved the marketing of Kayldeco for children as young as 1.

Other information

In Canada, where the minimum approved age for Kalydeco 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 ages 1 to 6, based on 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 the age of 1 is not approved. However, this is being investigated in the ARRIVAL study.

Ivacaftor is also available as 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.

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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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