Treatment with elexacaftor/tezacaftor/ivacaftor in children with cystic fibrosis (CF) may lead to a significant reduction in sweat chloride concentration and lung clearance index, and it appears equally safe and well-tolerated as in older age groups, according to a study published in the American Journal of Respiratory and Critical Care Medicine.

In this phase 3, open-label, 2-part study, researchers evaluated the safety, pharmacokinetics, pharmacodynamics, and efficacy of elexacaftor/tezacaftor/ivacaftor in children with CF aged 2 through 5 years. 

“Elexacaftor/tezacaftor/ivacaftor has been shown to be safe and effective in people with CF aged ≥6 years with ≥1 F508del-CFTR allele but has not been studied in younger children,” Goralski and colleagues noted.

Children weighing less than 14 kg on day 1 received 80 mg of elexacaftor once per day, 40 mg of tezacaftor once per day, 60 mg of ivacaftor each morning, and 59.5 mg each evening. Children weighing 14 kg or more received a daily dose of elexacaftor 100 mg, a daily dose of tezacaftor 50 mg, and 75 mg of ivacaftor every 12 hours. 

In part A of the study, which lasted 15 days, the primary objectives were to assess pharmacokinetics, safety, and tolerability. The primary focus of part B, which spanned 24 weeks, was also on safety and tolerability, with secondary endpoints including pharmacokinetics, absolute changes from baseline in sweat chloride concentration and lung clearance index 2.5 (LCI2.5).

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The pharmacokinetic data from 18 participants enrolled in part A confirmed the appropriateness of the Part B dosing regimen, and 75 children were enrolled in part B. Sweat chloride concentration and LCI2.5 decreased from baseline through week 24, while mean body mass index (BMI) was within the normal range at baseline and remained stable through the end of part B.

According to the results, 74 children (98.7%) experienced either mild (62.7%) or moderate (36.0%) adverse events. The study authors reported cough, fever, and rhinorrhea as the most common adverse events.

Patients with CF develop abnormally thick mucus in the respiratory system, leading to persistent cough, bacterial infections, and shortness of breath. Excessive loss of salt through sweat may lead to dehydration, weakness, fatigue, cardiac arrhythmias, and even death.

Reference

Goralski JL, Hoppe JE, Mall MA, et al. Phase 3 open-label clinical trial of elexacaftor/tezacaftor/ivacaftor in children aged 2 through 5 years with cystic fibrosis and at least one F508del allele. Am J Respir Crit Care Med. Published online March 15, 2023. doi:10.1164/rccm.202301-0084OC