GLPG2737 + lumacaftor + ivacaftor

GLPG2737 + lumacaftor + ivacaftor is an experimental triple combination therapy targeting **cystic fibrosis (CF)** in patients homozygous for the F508del-CFTR mutation. This regimen builds on the standard lumacaftor/ivacaftor (Orkambi), a combination CFTR corrector (lumacaftor) and potentiator (ivacaftor), by adding GLPG2737, a small molecule type 2 corrector developed to act synergistically. - **Lumacaftor** is a C1 corrector that enhances CFTR protein processing and trafficking to the cell surface. - **Ivacaftor** is a potentiator that increases the opening probability (gating) of the CFTR chloride channel. - **GLPG2737** is a type 2 (C2) corrector acting via a mechanistically complementary pathway, providing additive restoration of CFTR function beyond dual therapy. Preclinical and phase 2a clinical data showed that the triple combination further improved sweat chloride and lung function measures in patients compared to lumacaftor/ivacaftor alone, indicating an increased activity of mutated CFTR. Developed by Galapagos, this combination has been investigated as a strategy to enhance clinical efficacy in cases where dual modulator therapy yields modest responses[1][3][4][8].

Brand names

Orkambi