FDA Approves Kalydeco for Treatment of 6- to 12-month-old Infants with Cystic Fibrosis

The U.S. Food and Drug Administration (FDA) has approved Kalydeco (ivacaftor) for the treatment of infants from six to 12 months old, who have cystic fibrosis (CF) and at least one mutation in the CFTR gene, announced the therapy’s developer, Vertex Pharmaceuticals.

With the potential to treat the underlying cause of CF, the twice-daily oral therapy is designed for CF patients with specific mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which results in the production of a defective CFTR protein and impaired movement of salts in and out of cells.

“Today’s approval for Kalydeco allows physicians to begin treating the underlying cause of CF in eligible infants as young as six months of age for the first time, with the potential to modify the course of the disease,” Margaret Rosenfeld, MD, of the Seattle Children’s Research Institute and department of pediatrics, University of Washington School of Medicine, said in a press release.

The U.S., Canada, and the European Union (EU) have so far approved Kalydeco for the treatment of CF children who are at least 12 months old.

The FDA made its decision to approve Kalydeco for the treatment of infants as young as six months based on results from a Phase 3 (ARRIVAL) trial (NCT02725567).

In the study, 11 toddlers with one of 10 mutations in the CFTR gene (G551D, G178R, S549N, S549R, G551S, G1244E, S1251N, S1255P, G1349D, or R117H) received Kalydeco for 24 weeks.

The study showed a similar safety profile in this age group to the one previously observed in a group of older children and adults, which showed mild or moderate adverse events in most cases. None of the participating children discontinued the treatment due to adverse events.

The most common adverse events observed in the study included cough (64%), stuffy nose (nasal congestion; 36%), and runny nose (rhinorrhea; 36%). Although three serious adverse events were reported in three patients, they were considered unrelated to Kalydeco treatment.

The investigators also compared the children’s sweat chloride concentrations — an indicator of malfunctioning CFTR protein — at the start of the study, and after 24 weeks. They found that Kalydeco treatment reduced the sweat chloride levels between baseline (mean concentration of 101.5 mmol/L or millimole per liter) and the end of the study (mean concentration of 43.1 mmol/L). Levels above 60 mmol/L are considered abnormal, and indicate a high likelihood of CF.

“The manifestations of CF are often present at birth, which underscores our relentless commitment to reach the youngest CF patients possible in our clinical trials,” said Reshma Kewalramani, MD, executive vice president, and chief medical officer at Vertex.

“As an important outcome of these efforts, we are now able to treat infants with cystic fibrosis as early as six months of age with Kalydeco,” she added.

The FDA first approved Kalydeco in the U.S. in 2012, and the treatment is now available in more than 40 countries.