Larazotide Acetate

Pharmaceutical

Larazotide acetate (formerly AT-1001) is a synthetic octapeptide derived from Vibrio cholerae zonula occludens toxin (Zot) that acts as a tight junction regulator in the intestinal epithelium. It was developed by Alba Therapeutics (later acquired by Innovate Biopharmaceuticals, then 9 Meters Biopharma) as a first-in-class treatment for celiac disease. Unlike a gluten-free diet, which requires complete avoidance of gluten exposure, larazotide is designed to protect the intestinal barrier during inadvertent gluten ingestion by preventing the disassembly of tight junction protein complexes. The peptide works locally in the gut lumen — it is not systemically absorbed. When gluten-derived gliadin peptides reach the intestinal epithelium, they trigger zonulin release, which disassembles tight junctions and increases paracellular permeability. This allows gliadin fragments to cross the epithelial barrier and activate the immune response that drives celiac disease pathology. Larazotide blocks zonulin-mediated tight junction opening, maintaining epithelial barrier integrity and reducing the downstream inflammatory cascade. Larazotide has progressed through multiple Phase II trials and into Phase III evaluation for celiac disease, making it one of the most clinically advanced peptide-based gut therapeutics. In Phase IIb trials, larazotide significantly reduced celiac disease symptoms (abdominal pain, bloating, diarrhea) and decreased anti-tissue transglutaminase (anti-tTG) antibody levels compared to placebo in patients on a gluten-free diet experiencing ongoing symptoms. The 0.5 mg three-times-daily dose showed the most consistent efficacy signal. Its potential application extends beyond celiac disease to other conditions associated with increased intestinal permeability, including inflammatory bowel disease, type 1 diabetes, and irritable bowel syndrome, though clinical data for these indications remains early-stage.