The CFTR modulator therapy ivacaftor (Kalydeco) may be safely used in the first year of life to treat the underlying cause of cystic fibrosis, latest results from the ARRIVAL study suggest.

Currently listed on the PBS for use in children from 12-24 months of age, newly-published findings show the drug can be safely dosed in children aged  four months to 12 months of age.

The results, from 25 infants with a CFTR gating mutation enrolled in the ARRIVAL trial, indicated that the pharmacokinetics and safety profile of ivacaftor were similar to that seen in older children who received the drug.

And preliminary findings of improvements in sweat chloride levels and markers of  pancreatic function also suggest the drug will be effective in modulating the course of CF, the study investigators said.

Published in the American Journal of Respiratory and Critical Care Medicine, the findings from the ongoing ARRIVAL study relate to infants aged four months to 12 months of age who were given 25 mg or 50 mg ivacaftor every 12 hours for 24 weeks.

The investigators noted that ivacaftor was well tolerated, and most adverse events were mild/moderate. There were no serious adverse events related to the drug and no withdrawals due to treatment related adverse events. One infant had an alanine transaminase elevation >3 to ≤5 × upper limit of normal at week 24. No other adverse trends in laboratory tests, vital signs, or electrocardiogram parameters were reported.

Sweat chloride levels improved by a mean of −55.7 mmol/L at week 24, comparable to improvements seen in older children. The mean sweat chloride level of 41.3 mmol/L was below the threshold for CF and in the range for residual CFTR function.

Similarly, mean improvements of 166.0 μg/g in levels of FE-1, a biomarker of exocrine pancreatic function were seen in the study. At baseline, 11 infants had baseline FE-1 concentrations of ≤200 μg/g, indicating pancreatic insufficiency, among whom seven of 9 with paired data had regained pancreatic sufficiency at week 24. Measures of lipase and amylase – also markers of pancreatic function were consistent with those seen in older children taking ivacaftor, suggesting the potential of ivacaftor to delay or minimise progressive exocrine pancreatic dysfunction

The study investigators in the Vertex-funded study  – including Professor Claire Wainwright, Head of Cystic Fibrosis Service at the Royal Children’s Hospital in Brisbane –  cautioned that their findings came from a small sample size of children but said they were consistent with the established safety profile in older children.

“Ivacaftor has a favourable safety profile; it was well tolerated at both doses tested, with no new safety concerns … This study of ivacaftor in the first year of life supports treating the underlying cause of cystic fibrosis in children aged ≥4 months with ≥1 gating mutation,” they concluded.