The US Food and Drug Administration (FDA) has approved the use of lumacaftor/ivacaftor (Orkambi®) in children with cystic fibrosis who are aged 12 to 24 months. 

In a press release from Vertex, the developers of lumacaftor/ivacaftor, chief medical officer Carmen Bozic, MD, said that treating patients at an early age is of great importance, as this may delay the progression of the disease.

Lumacaftor/ivacaftor was already approved for the treatment of patients with cystic fibrosis who are aged 2 years and above and have 2 copies of the F508del mutation. The approval of the treatment in younger children is based on the results of a phase 3 clinical trial in 46 children that showed that the treatment was generally well tolerated and that its safety profile and pharmacokinetics were similar to what was observed in older children.

Cystic fibrosis is caused by a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. This gene encodes a channel protein that controls the passage of salts and water across cell membranes. 

Read more about disease-modifying therapies for cystic fibrosis

There are different types of mutations that cause various defects in the CFTR protein. Some of these lead to no CFTR protein being made, while others cause the protein to misfold so that it cannot be transported to the cell membrane. In other cases, the protein is transported to the cell membrane but is “stuck closed,” has decreased conductance (ie, can transport only a small amount of chloride ions), or is degraded too quickly once at the cell surface. 

CFTR modulator treatment that can address these problems (apart from the complete absence of CFTR protein) exists. These include potentiators that “prop open” the gate and correctors that help the CFTR protein fold correctly. Ivacaftor is a potentiator, while lumacaftor and tezacaftor are correctors. 

Lumacaftor/ivacaftor is a combination therapy that includes both a potentiator and a corrector, so it increases the amount of CFTR protein at the cell surface as well as its ability to transport salt and water across the membrane.

The results from the trial in children aged 12 to 24 months showed that lumacaftor/ivacaftor also reduced sweat chloride concentration, suggesting it had therapeutic effects.


Vertex announces U.S. FDA approval for Orkambi® (lumacaftor/ivacaftor) in children with cystic fibrosis ages 12 to <24 months. News release. Vertex Pharmaceuticals Incorporated; September 2, 2022.