Ivacaftor Safe and Effective for Infants with Cystic Fibrosis Aged 1 to <4 Months, reveals study

Ivacaftor had previously exhibited evidence of safety and efficacy in children ≥4 months of age with CF and CFTR gating variants. This study was conducted so as to extend those findings by investigating the safety, PK, and efficacy of IVA in infants aged 1 to <4 months with CF and an IVA-responsive CFTR variant.

The study included seven infants with CF, aged 1 to <4 months, who received an initial low dose of IVA based on age and weight. Given the sensitivity of IVA as a CYP3A substrate and the uncertain maturation of CYP3A in infants, doses were adjusted at day 15 based on individual PK measurements taken on day 4. The primary endpoints were safety and PK measurements.

The key findings of the study were:

• Seven infants (five with residual function CFTR variants and two with minimal function CFTR variants) received at least one dose of IVA. Six had doses adjusted at day 15, while one infant did not require adjustment.

• Subsequent PK analyses indicated that mean trough concentrations for IVA and its metabolites were within the range of prior clinical experience.

• Four infants had AEs, but no serious AE was recorded.

• One infant had to be withdrawn from the study drug because of an AE of ALT greater than 8 times the ULN, which was assessed as non-serious.

• At week 24, the reduction in mean sweat chloride concentration was 40.3 mmol/L, with an SD of 29.2.

• This was accompanied by an improvement in biomarkers of pancreatic function and intestinal inflammation, and growth parameters also improved.

This small, open-label study showed that IVA dosing in infants ensured exposures previously demonstrated to be safe and effective. The predictable PK allowed for a dose disturbance by age and weight. More generally, IVA was well tolerated and resulted in significant improvements in CFTR function, markers of pancreatic function, intestinal inflammation, and growth parameters.Results that reinforce the use of IVA in infants as young as 1 month old, conclusively representing Ivacaftor as safe and efficient for infants less than 4 months with CF and so, therefore, is a viablely efficient treatment for this very young population.

Reference:

McNally, P., Singh, A., McColley, S. A., Davies, J. C., Higgins, M., Liu, M., Lu, J., Rodriguez-Romero, V., Shih, J. L., & Rosenfeld, M. (2024). Safety and efficacy of ivacaftor in infants aged 1 to less than 4 months with cystic fibrosis. Journal of Cystic Fibrosis: Official Journal of the European Cystic Fibrosis Society, 23(3), 429–435. https://doi.org/10.1016/j.jcf.2024.03.012