A tight junction regulator in Phase 3 trials for celiac disease — the first drug to target intestinal permeability directly.
Larazotide acetate (AT-1001) is an octapeptide derived from Vibrio cholerae zonula occludens toxin (Zot). It acts as a tight junction regulator that prevents the opening of intestinal tight junctions triggered by gliadin (a component of gluten). By maintaining tight junction integrity, larazotide reduces intestinal permeability — the 'leaky gut' phenomenon implicated in celiac disease.
Developed by Innovate Biopharmaceuticals (later 9 Meters Biopharma), larazotide is the most clinically advanced drug targeting intestinal permeability. It does not prevent gluten ingestion or digestion, but rather blocks the downstream permeability effects that trigger the celiac immune response.
Larazotide has completed Phase 2 trials and entered Phase 3 for non-responsive celiac disease (patients who continue to have symptoms despite a gluten-free diet). If approved, it would be the first pharmacological treatment for celiac disease.
Phase 2b trials demonstrated significant reduction in celiac symptoms (abdominal pain, bloating, diarrhea) in patients on a gluten-free diet who still experienced symptoms. The drug reduced intestinal permeability markers and improved patient-reported outcomes. The optimal dose was 0.5 mg three times daily.
The mechanism is unique: larazotide blocks zonulin-mediated tight junction opening without systemic absorption — it acts locally in the gut lumen. This local action provides an excellent safety profile with minimal systemic side effects.
📚 Key Reference: PMID: 25803399 (Phase 2b celiac disease)
Excellent safety profile in clinical trials due to minimal systemic absorption. Acts locally in the gut lumen. Most common side effects were GI-related (mild nausea, headache) and comparable to placebo. No significant drug interactions identified. Consult your provider.
NOT FDA-approved. In Phase 3 clinical trials for celiac disease. Orphan Drug and Fast Track designations from FDA. Would be first-in-class if approved.