Vertex broke new ground in 2012 when regulators approved its ivacaftor as the first disease-modifying cystic fibrosis drug. But this initial approval was only for use in the ∼4% of cystic-fibrosis patients that have G551D mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) ion channel. With the US Food and Drug Administration (FDA)'s approval of Vertex's combination of ivacaftor plus lumacaftor in July, the treatment-eligible population expands to include patients with the most common CFTR mutation, F508del, which accounts for close to 50% of disease cases. For now, the combination is only approved in patients aged 12 years and older, but ongoing trials in patients as young as 6 could further expand its utility.

By combining lumacaftor, which stabilizes CFTR during the folding process, with ivacaftor, which potentiates the activity of CFTR at the cell surface, Vertex has succeeded in restoring some CFTR function. In pivotal trials, combination treatment improved measures of forced expiratory volume in 1 second by about 3% over placebo at 24 weeks. Before the approval, there were some concerns that this effect was too modest (Nat. Rev. Drug Discov. 13, 713–714; 2014). But in May an independent panel of FDA advisors voted 12 to 1 in favour of approving the combination therapy.

Analysts are forecasting peak global annual sales of the combination of US$3.8 billion by 2019, according to a consensus sales estimate from Thomson Reuters Cortellis.

Vertex's VX-661, a follow-on to lumacaftor that also stabilizes CFTR during its folding, is in Phase III trials. Several other cystic fibrosis candidates, including a gene therapy, are also in development (Nat. Rev. Drug Discov. 13, 721–722; 2014).