Background：Andecaliximab formerly GS-5745; Gilead Sciences, Inc., a recombinant chimeric IgG4 monoclonal antibody mAb, was engineered to remove T-cell epitopes to reduce immunogenicity risk. Andecaliximab selectively binds and inhibits matrix metalloproteinase-9 MMP9 with minimal cross-reactivity to other matrix metalloproteinases, including the highly homologous matrix metalloproteinase-2 MMP-2. Andecaliximab is under development for the treatment of cystic fibrosis, gastric cancer, pancreatic cancer, non-small cell lung cancer NSCLC, rheumatoid arthritis RA, Crohn's disease CD, and ulcerative colitis UC. In a recent phase 1 dose-escalation study in patients with UC, andecaliximab had good tolerability and was associated with a numerically greater percentage of clinical, endoscopic, and histological responses in patients relative to placebo over a 5-week treatment period. A phase 2/3 trial, evaluating the safety and efficacy of andecaliximab to induce and maintain clinical remission in patients with moderate to severe UC, was initiated. A planned interim futility analysis following an 8-week induction period in the first 150 patients resulted in the termination of the study due to lack of efficacy.
