Kalydeco (ivacaftor) is a treatment developed and commercialized by Vertex Pharmaceuticals for cystic fibrosis (CF) patients with any one of 33 CFTR gating mutations. The medication is approved by the U.S. Food and Drug Administration for patients ages 2 and older, and is also available in Europe, Canada, Australia, and New Zealand.

Kalydeco is a potentiator, or agent, that enhances the activity of the CF transmembrane conductance regulator (CFTR), a protein found on cell membranes. It was the first drug to address the underlying causes of the disease, instead of only treating its symptoms. The oral medication was approved by the FDA in January 2012 to treat adults and children age 6 and older with specific gating mutations (one of 10) in the CF gene. 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 above.

A new Phase 3 study (NCT02725567), beginning in the U.S. and elsewhere, is evaluating Kalydeco in infants and toddlers with CF and one of nine CFTR gating mutations.

History of Kalydeco

The efficacy of Kalydeco was evaluated by Vertex, a Massachusetts-based pharmaceutical company, in two randomized, double-blind, placebo-controlled clinical trials, which were used to justify the FDA’s approval. The studies included 213 individuals who were treated with 150 mg of Kalydeco or placebo twice daily (every 12 hours), together with their 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 one 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, which was also used to support FDA approval. The agency approved Kalydeco in 2012 to treat patients age 6 and older based on this data, and later approved a granulated version for children 2 to 5 years old based on additional studies.

KalydecoHow Kalydeco works

The unique mechanism of action of Kalydeco revolutionized CF treatment by address the underlying cause of the disease, a genetic defect in the gene encoding for the CFTR protein. Due to this mutation, patients develop a thick and sticky mucus in the respiratory, digestive and reproductive systems. Kalydeco works to keep CFTR proteins at the cell surface open 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.)

Other details about Kalydeco

Kalydeco was originally approved to treat CF caused by the G551D mutation, which is present in approximately 4 percent 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 two and older) and that mutation was added in Canada (for patients ages 18 and older).

Most recently, in May 2017, the FDA further expanded the use of Kalydeco to treat 23 additional mutations of the CFTR gene in patients ages 2 and older, bringing the number of CF-causing gene mutations treatable with Kalydeco to 33 — almost three times the number of mutations  previously treatable with the drug. As a result, Kalydeco can now be used to treat nearly 2,800 people, about 10 percent of all CF patients in the U.S.

The FDA based its decision on laboratory tests (showing a positive response to the drug) combined with Kalydeco’s benefits observed in earlier clinical trials. This approach was adopted since many rare CFTR mutations have very small patient populations, making it difficult to conduct clinical studies. 

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

Kalydeco is also being studied in a new Phase 3 clinical trial (NCT02725567) in about 35 children with CF under age 2 (newborns to toddlers) and with one of nine CFTR mutations, testing the drug’s safety, pharmacokinetics and pharmacodynamics. The two-part, open-label study is now recruiting across the U.S., and in Canada, Australia, and expects to conclude in September 2018.

Kalydeco drug indications

In Canada, where the minimum age to use Kalydeco is 6 years, Kalydeco 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 for elevated levels of liver enzymes, called transaminases, as well as cataracts in children.

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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