| 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. |
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