Early Kalydeco Therapy Shown to Benefit 2 CF Infants: Case Study
Kalydeco (ivacaftor) therapy, given before age 1, was shown to normalize sweat chloride levels, and improve growth and lung and pancreas function in two baby boys with cystic fibrosis (CF), a case study reported.
According to the researchers, these results show that Kalydeco “seems to be safe and efficacious for infants [younger than] 12 months of age. The results underline the early and sustainable effect of [Kalydeco], indicated especially by sweat chloride … and … pancreas function.”
The study, “REAL-world clinical effectiveness of ivacaftor therapy in the first 24 months in two infants with cystic fibrosis and different gating mutations – A case report,” was published in the journal Clinical Case Reports.
CF is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which produces “gate” CFTR proteins that regulate the flow of water and salts in and out of cells. A CFTR protein that does not work properly causes the buildup of sticky mucus in various organs. In patients with a gating mutation, the faulty CFTR gate is stuck closed.
Kalydeco, a CFTR modulator marketed by Vertex Pharmaceuticals, works by keeping the gate open for longer in patients with a gating mutation. In Austria, where these patients were treated, it is approved for treating individuals ages 12 months and older with a gating mutation.
This case study investigated the treatment of two boys, both younger than 1 year, with Kalydeco. The infants had different gating mutations. Notably, Kalydeco for these two infants was started off-label, meaning the therapy was used for patients it is not approved to treat.
The CF diagnosis was based on the measurement of sweat chloride — a marker of CFTR function that measures the amount of salt in a person’s sweat — in the second month of life. Fecal elastase, a marker of pancreas function, was low and growth was impaired in both boys. That prompted the start of Kalydeco therapy at a dose of 50 mg twice per day at 2 months in one boy and at 11 months in the other.
Subsequently, the researchers assessed sweat chloride, lung function, and pancreas function on day 14, week 4, week 16, and months 10, 17 and 24 (two years) of treatment. The infants’ growth and nutrition status also was assessed at those time points.
The first child responded rapidly to treatment, attaining normal sweat chloride levels after two weeks and normal pancreas function after four weeks. He also experienced improvements in lung function. The boy also had increased vitamin levels, and stopped taking digestive enzymes after four weeks of treatment, as well as eliminating vitamin supplements except vitamin D. Growth progress was insufficient and nutrition status improved toward the end of the study.
In the second child, sweat chloride levels declined and remained low until month 10, remaining within normal values thereafter. Lung function remained normal from week 14 to week 24 (just short of six months). Pancreatic function, as assessed by fecal elastase, began to increase after week 16, and by the seventh month pancreatic enzymes were withdrawn. Vitamin supplements were also stopped by month 10. Growth and weight gains were below the age average.
“In this study, we compared effects of [Kalydeco] in two patients with different genetic statuses: patient 1 presenting with S549N, a non-G551D gating variant, patient 2 with G551D, the most common CFTR gating mutation,” the scientists wrote. “Reduction in sweat chloride and improvement of FE [fecal elastase] in patient 1 start earlier in therapy and seem to have a strong instant effect, whereas impact of [Kalydeco] in patient 2 is delayed. Also, effect on growth velocity is more present in patient 1.”
Notably, both infants maintained the improvements in sweat chloride levels and in lung and pancreas function, and did not experience side effects, according to a laboratory analysis.
“Highly efficient modulators are able to maintain pancreatic function, especially when therapy is started early in life, and therefore, pancreatic substitution therapy can be successfully terminated,” the researchers wrote.
“CFTR modulation with the highly effective CFTR modulator [Kalydeco] is clearly disease modifying,” they wrote, adding that the therapy “could be reconsidered” in these patients.
The scientists recommended further long-term studies of Kalydeco and analyses in children younger than 1 year.