Vertex preclinical data

Data from a pair of in vitro studies published in Science Translational Medicine showed that Vertex’s Kalydeco ivacaftor reduced the correction efficacy of the company’s lumacaftor to treat CF in human cells with 2 copies of the delta F508 mutation in the CF transmembrane conductance regulator ( CFTR) gene. Lumacaftor is a small molecule CFTR corrector that works by partially restoring the defects caused by the delta F508 CFTR mutation to increase functional expression of the protein. Kalydeco is a small molecule potentiator of CFTR that works by improving gating defects caused by other CFTR mutations.

The in vitro studies showed that in cells with 2 copies of the delta F508 CFTR mutation, Kalydeco impaired the biochemical stability of the mutant CFTR, leading to reduced expression of lumacaftor-corrected delta F508 CFTR protein on the plasma membrane. In one study, researchers at McGill University and colleagues said the data suggest that further optimization of potentiators may improve the clinical benefit of CFTR potentiator/corrector combinations. The second study was conducted by researchers at the University of North Carolina at Chapel Hill. ...