Cystic fibrosis drug ivacaftor benefits pre-school children

by Bruce Sylvester: Ivacaftor appears to be safe and efficacious for children ages 2 to and 5 with a specific type of cystic fibrosis, researchers reported  on  Jan. 20,2016 in The Lancet Respiratory Medicine. The findings suggest a therapeutic opening in early life when eventual organ damage from cystic fibrosis might be reduced.

Lead investigator professor Jane Davies from the National Heart and Lung Institute at Imperial College London, London, UK, said, “This was a small trial, but we are thrilled to see these results. Ivacaftor is a potential new treatment to offer children aged 2 years and older with cystic fibrosis and a CFTR gating mutation. This novel therapy could substantially impact on these children’s lives, potentially opening the way to even greater progress in years to come.”

Ivacaftor targets the basic defect of cystic fibrosis, seen in about 4% of cystic fibrosis patients with at least one mutation in the CFTR/ cystic fibrosis transmembrane conductance regulator gene.

Earlier studies confirmed that ivacaftor is safe and effective in children over 6, adolescents, and adults with these so called “gating” mutations. The drug is approved for use for these patients. This is the first study of its effects on younger children.

The investigators enrolled 34 pre-school children with cystic fibrosis aged between 2 and 5 years and with at least one copy of a mutation in the CFTR gene. They received the drug at one of two doses (50mg for children with bodyweight <14 kg and 75mg for ≥14 kg) twice daily for 6 months.

The 34 subjects who completed the 6-month treatment achieved significant reductions in sweat chloride levels, showing improvement in ability to restore the balance of salt in and out of cells, the process which when defective leads to cystic fibrosis.

They also achieved improved weight gain that could provide protection against eventual decline in nutritional status and better lung function in later childhood.

Notably, over a quarter of the subjects rose above the clinical cut off for pancreatic insufficiency at least once during treatment. This suggests, the authors said, “a window in early life where at least partial restoration of pancreatic function might be possible.”  This is the first time that this potential has been suggested by any drug treatment  in cystic fibrosis patients.

Ivacaftor was generally well tolerated with a safety profile similar to that seen in adults.