A study published in the 'American Journal of Respiratory and Critical Care Medicine' illustrated favorable safety and tolerability profile of Elexacaftor/Tezacaftor/Ivacaftor (ELX/TEZ/IVA) in children suffering from cystic fibrosis. Researchers sought to determine the long-term safety and effectiveness of ELX/TEZ/IVA. The phase 3, two-part (Part A and Part B), open-label extension study included children 6 years of age or older, diagnosed with cystic fibrosis who had F508del and a minimal function cystic fibrosis transmembrane conductance regulator (CFTR) mutation (F/MF genotypes) or were homozygous for F508del (F/F genotype).

Participants who completed the 24-week parent study were administered ELX/TEZ/IVA based on their weight. Those weighing less than 30 kg were given 100 mg ELX once a day, 50 mg TEZ once a day, and 75 mg IVA every 12 hours, while children weighing 30 kg or more were administered 200 mg ELX once a day, 100 mg TEZ once a day, and 150 mg IVA every 12 hours (adult dose).

A total of 64 children (36 with F/MF genotypes and 28 with F/F genotypes) participated in the study and received at least one dose of ELX/TEZ/IVA. The mean duration of exposure to ELX/TEZ/IVA was 93.9 (standard deviation: 11.1) weeks.

The major endpoint of the study was to determine the tolerability and safety of the intervention. The observed adverse events and serious adverse events were in line with common symptoms of cystic fibrosis disease. Overall, the rates of adverse events and serious adverse events (adjusted for exposure) were lower in the study (407.74 and 4.72 events per 100 patient-years, respectively) compared to the parent study (987.04 and 8.68 events per 100 patient-years, respectively). Only one child (1.6% of the participants) experienced an adverse event of aggression, which was of moderate severity but resolved after discontinuing the study drug.

Compared to the baseline of the parent study at Week 96, the mean percentage of predicted forced expiratory volume in one second (ppFEV1) elevated by 11.2 percentage points in the extension study. Additionally, there was a decrease in sweat chloride concentration by -62.3 mmol/L, an improvement of 13.3 points in the Cystic Fibrosis Questionnaire-Revised respiratory domain score, and a reduction of -2.00 units in lung clearance index 2.5 (LCI2.5).  The study also observed an elevation in growth parameters.

The estimated rate of pulmonary exacerbations per 48 weeks was 0.04. The annualized rate of alteration in ppFEV1 was 0.51 percentage points per year. Throughout an additional 96 weeks of intervention, ELX/TEZ/IVA was promising in children aged six years and above. The improvements in CFTR function, respiratory symptoms, and lung function that were initially observed in the parent study were sustained. These findings provide evidence of the long-term safety profile and long-lasting clinical advantages of ELX/TEZ/IVA in the specific group of pediatric patients.