Elexacaftor

Cystic fibrosis (CF) is the result of a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The CFTR proteins produced by this gene are transmembrane ion channels that move sodium and chloride across cell membranes - water follows the flow of chloride ions to the cell surface, which consequently helps to hydrate the surface of the cell and thin the secretions (i.e. mucous) around the cell. Mutations in the CFTR gene produce CFTR proteins of insufficient quantity and/or function, leading to defective ion transport and a build-up of thick mucous throughout the body that causes multi-organ disease involving the pulmonary, gastrointestinal, and pancreatic systems (amongst others). The most common CFTR mutation, the F508del mutation, is estimated to account for 70 to 90% of all CFTR mutations and results in severe processing and trafficking defects of the CFTR protein.

Elexacaftor is a CFTR corrector that modulates CFTR proteins to facilitate trafficking to the cell surface for incorporation into the cell membrane. The end result is an increase in the number of mature CFTR proteins present at the cell surface and, therefore, improved ion transport and CF symptomatology. Elexacaftor is used in combination with tezacaftor, another CFTR corrector with a different mechanism of action, and ivacaftor, a CFTR potentiator that improves the function of CFTR proteins on the cell surface - this multi-faceted, triple-drug approach confers a synergistic effect beyond that seen in typical corrector/potentiator dual therapy regimens.