Kalydeco Seen as Safe in Treating Young Children, Ages 1 to 2, in Phase 3 Trial, Vertex Reports

Kalydeco (ivacaftor) is safe and effective in 1- and 2-year-olds with cystic fibrosis (CF), Vertex Pharmaceuticals reported based on data from its ongoing Phase 3 clinical trial in infants and toddlers.

The treatment’s safety was similar to that seen in studies of older children, the company said. Moreover, the treatment improved sweat chloride levels — indicating its effectiveness in treating CF also in children as young as one year.

The results prompted Vertex to start preparing regulatory requests in the U.S. and E.U. for Kalydeco to also be approved to treat children between the ages of 1 and 2 years. The company plans to submit its applications in early 2018.

“We know that cystic fibrosis is a progressive disease with organ damage already present at birth, so the earlier patients can begin treatment, the greater their potential for improved outcomes,” Jane Davies, MD, co-lead investigator of the study at Royal Brompton Hospital and Imperial College London, said in a press release.

“These results are incredibly exciting: they suggest that we can begin treating the underlying cause of cystic fibrosis with Kalydeco in children as young as one year of age,” Davies added.

The trial continues to explore if Kalydeco can be used also in infants.

The Phase 3 trial, called ARRIVAL (NCT02725567), is an open-label study performed in two parts. It is enrolling children, under the age of two, with one of 10 so-called gating mutations that prevent the CFTR chloride channel from opening properly. Kalydeco treats CF by helping the channel to open.

In the first part of the study, children are treated with Kalydeco for five days to allow researchers to assess the treatment’s safety. Since infants and small children can process drugs differently from older children and adults, scientists are also examining how the drug behaves in the body — measures referred to as pharmacokinetics.

Patients who complete the first part may continue in the second part, which involves treatment for 24 weeks. In addition to evaluating safety and pharmacokinetics over the six months of treatment, researchers are studying Kalydeco’s effectiveness.

The study, which is still recruiting patients at sites across the U.S., Australia, Canada, Ireland and the U.K., is designed so that increasingly younger children are being enrolled only when the assessment of older groups is done. Information is available by clicking on the trial’s identification number.

In addition to showing that Kalydeco improved sweat chloride levels, exploratory analyses found the treatment also improved the children’s pancreatic function — which is typically impaired in CF patients.

Kalydeco was generally well-tolerated with a safety profile similar to that seen in earlier studies in children older than 2 years.

“We have a significant body of evidence demonstrating Kalydeco’s immediate and long-term benefits and its potential to modify the course of CF,” said Jeffrey Chodakewitz, executive vice president and chief medical officer at Vertex.

“These results are an important step in our goal of treating children as early as possible to intervene in this progressive disease,” Chodakewitz added.

Kalydeco is already approved for children with CF ages 2 or older who have one of 38 specific mutations in the CFTR gene. The latest approval, in August 2017, added five so-called splicing defect mutations to the list.