Young children with cystic fibrosis treated with a combination of the CFTR-correcting therapies ivacaftor (Kalydeco) and lumacaftor (Orkambi) have seen rapid improvements in their symptoms in a phase III randomised controlled trial.
The fixed dose combination treatment with lumacaftor (100mg) and ivacaftor (125mg) improved the lung clearance index (LCI2.5) and sweat chloride concentrations in 6-11 year olds, homozygous for the F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.
The trial, reported in The Lancet Respiratory Medicine also found the treatment was also well tolerated compared with placebo.
The researchers said their findings supported the early initiation of CFTR correcting therapy to help preserve lung function in young children with cystic fibrosis.
“This finding is consistent with the previous observation in older patients that lumacaftor and ivacaftor has a disease-modifying effect on the progressive decline in lung function associated with cystic fibrosis.”
“This conclusion is of particular importance in paediatric patients for whom the preservation of lung function is a primary goal in clinical practice,” they wrote.
The study, run across 54 centres and nine countries including Australia, recruited just over 200 eligible patients for either daily oral treatment or placebo for 24 weeks.
Statistically significant improvements in LCI2.5 from baseline and compared to controls were apparent from day 15 and sustained throughout the study duration.
Sweat chloride concentrations also declined significantly by day 15 and persisted at low levels throughout the study.
The researchers said the sweat chloride result provide a mechanistic validation to the pulmonary findings as it represents ‘an improvement in CFTR function in response to modulator therapy’.
The study found no difference between the treatment and control groups in rates of either adverse events (95 v 97%) or serious adverse events (13 v 11%).
An accompanying Comment, published in The Lancet Respiratory Medicine, said CFTR correcting therapies were shifting the clinical focus from largely symptom management to a more precision medicine approach based on the underlying mutations.
It said current therapies including airway clearance, inhaled mucolytics and the prevention or prompt treatment of infections were insufficient to prevent irreversible structural damage to the lungs.
The study was funded by Vertex pharmaceuticals.