Kalydeco (ivacaftor) is a treatment developed and commercialized by Vertex Pharmaceuticals for the treatments of cystic fibrosis (CF) in patients ages 2 and older with one of 38 CF transmembrane conductance regulator (CFTR) gating mutations. The medication is approved by the U.S. Food and Drug Administration (FDA) for patients ages 2 and older and also is available in Europe, Canada, Australia, and New Zealand.

The therapy also is being evaluated in infants and toddlers with CF and those with one of nine additional CFTR gating mutations.

How Kalydeco works

Kalydeco is a potentiator, or agent, that enhances the activity of the CF transmembrane conductance regulator (CFTR) gene, a protein found in cell membranes. Due to CFTR mutation, patients develop a thick and sticky mucus in the respiratory, digestive, and reproductive systems. Kalydeco works to keep the CFTR open at the cell surface to facilitate the transport of salt and water through cells, improving hydration and mucus clearance. (In gating mutations, the sodium channel does not open as it should.)

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

History of Kalydeco

Kalydeco’s effectiveness was evaluated by Vertex in two randomized, double-blind, placebo-controlled clinical trials cited in the FDA’s approval. The studies included 213 participants treated with 150 mg of Kalydeco or a placebo twice daily (every 12 hours), together with prescribed CF therapies. The studies supported Kalydeco’s safety and superiority in improving lung function as measured by FEV1 (the amount of air a person can forcibly exhale in 1 second). Improvements were persistent through 48 weeks of follow-up.

The company also conducted a double-blind, placebo-controlled, cross-over trial with 39 adult patients to assess different doses of the drug. Based on this data, the FDA approved the use of Kalydeco in January 2012 to treat adults and children ages 6 and older with a specific gating mutation in the CF gene. This is called the G551D mutation, which is present in approximately 4% of the 30,000 CF patients in the U.S.

In February 2014, Kalydeco’s indication was expanded to treat eight additional CFTR mutations — G178R, S549N, S549R, G551S, G1244E, S1251N, S1255P, and G1349D — found in approximately 150 people. In Canada, in addition to these eight mutations, the treatment was also indicated for patients with the G970R mutation.

At the end of 2014, the FDA added an additional mutation — R117H — to the list of Kalydeco’s use in the U.S. (in patients ages 6 and older) and that mutation was also included in Canada for patients ages 18 and older.

In March 2015, new research led the FDA to approve its use in younger children with these same mutations, and in May 2017, another 23 mutations were added to those treatable with Kalydeco in patients ages 2 and older, bringing the number of CF-causing gene mutations treatable by Kalydeco to 33 — almost three times the number of mutations previously treatable with the therapy.

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.  

The therapy 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 August 2017 approval was based on the results of the Phase 3 EXPAND study in which Kalydeco as a monotherapy arm met its primary efficacy endpoint and was generally well tolerated. EXPAND was an eight-week crossover study that 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 improvement in lung function with the combination treatment as well as Kalydeco monotherapy.   

Kalydeco indications

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 now 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.

The future

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, testing the drug’s safety, pharmacokinetics, and pharmacodynamics. The two-part, open-label study is now recruiting participants across the U.S., Canada, and Australia, and is expected to be concluded in September 2018.

The manufacturers are planning tests that might add more CFTR mutations to the list of mutations treatable with Kalydeco.

Note: 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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