N. Engl. J. Med. 379, 1599–1611 (2018)

N. Engl. J. Med. 379, 1612–1620 (2018)

A combination of therapies shows potential to treat up to 90% of individuals affected with cystic fibrosis.

Cystic fibrosis is caused by mutations in the membrane transporter cystic fibrosis transmembrane conductance regulator (CFTR). The common Phe508del mutation results in diminished amounts of protein at the cell surface and reduced efficiency of anion transport. The tezacaftor–VX-659 combination increases trafficking of mature CFTR to the cell surface, and ivacaftor augments the anion transport of mutant CFTR at the cell surface.

A group of researchers named the VX16-659-101 Study Group found that the combination of these therapies not only was effective at restoring Phe508del in vitro, but also shows substantial efficacy in individuals carrying one or two copies of Phe508del in a clinical trial, as measured by lung function, quality of life and sweat chloride, a marker of CFTR activity in patients. Very similar results were demonstrated with a related combination of medicines, VX-445–tezacaftor–ivacaftor.