Tezacaftor

Tezacaftor (VX-661) is an oral medication for cystic fibrosis (CF) developed by Vertex Pharmaceuticals. In a combination therapy formulation called Symdeko (tezacaftor plus ivacaftor), it is approved in the U.S. and Canada for CF patients, ages 12 and older, who have two copies of the F508del mutation in the CFTR gene and one minimal function mutation. Symdeko is approved and marketed in the EU as Symkevi.Tezacaftor is not approved as a stand-alone treatment, but as part of a combination therapy.

Tezacaftor is used as a combination therapy with Ivacaftor for the treatment of patients with cystic fibrosis.

VX-661 is an investigational compound that promotes the maturation of delta F508 mutants of the cystic fibrosis transmembrane conductance regulator (CFTR). Delta F508 CFTR represents a class of CFTR mutation that is characterized by impaired processing of misfolded CFTR proteins and reduced accumulation of the protein at the cell surface. VX-661 is intended to facilitate trafficking of CFTR to the epithelial cell membrane. It may be combined with the CFTR potentiator ivacaftor (Item No. 15145) to stimulate both CFTR accumulation and opening at the apical epithelial surface.

The transport of charged ions across cell membranes is normally achieved through the actions of the cystic fibrosis transmembrane regulator (CFTR) protein. This protein acts as a channel and allows for the passage of chloride and sodium. This process affects the movement of water in and out of the tissues. It impacts the production of mucus that lubricates and protects certain organs and body tissues, including the lungs. In the F508del mutation of the CFTR gene, one amino acid is deleted at position 508. Therefore, the CFTR channel function is compromised, resulting in thickened mucus secretions. CFTR correctors such as tezacaftor aim to repair F508del cellular misprocessing. This is done by modulating the position of the CFTR protein on the cell surface to the correct position, allowing for adequate ion channel formation and increased water and salt movement through the cell membrane. The concomitant use of ivacaftor is intended to maintain an open channel, increasing the transport of chloride and reducing thick mucus production.