Larazotide

Summary

Larazotide acetate (AT-1001) is an oral peptide in clinical development primarily for celiac disease. It targets the zonulin pathway to maintain intestinal barrier integrity, reducing gluten-induced tight junction permeability and associated inflammatory responses. Phase 2 clinical trials showed some efficacy in reducing gastrointestinal symptoms in celiac disease patients on a gluten-free diet who experience breakthrough symptoms.

Mechanism of Action

Larazotide acetate is a synthetic 8-amino acid peptide derived from Zonula occludens toxin (ZOT) of Vibrio cholerae. It acts as a tight junction regulator by antagonizing the zonulin receptor, thereby preventing zonulin-mediated opening of intestinal tight junctions and reducing intestinal permeability ('leaky gut').

Routes of Administration

Goals & Uses

• Adjunct to gluten-free diet in celiac diseaseDisease ManagementModerate
• Reduce gastrointestinal symptoms in celiac diseaseSymptom ManagementModerate
• Treatment of type 1 diabetes (experimental)Autoimmune DiseaseLow
• Attenuation of gluten-induced immune activationImmunomodulationLow
• Reduce intestinal permeability in celiac diseaseGastrointestinal Barrier FunctionModerate

Contraindications

• Known hypersensitivity to larazotide or any excipientAllergyHigh

Adverse Effects

• HeadacheNeurologicCommonPain in the head or upper neck
• NauseaGastrointestinalUncommonFeeling of sickness or urge to vomit
• Upper respiratory tract infectionInfectiousUncommon
• DiarrheaGastrointestinalUncommonLoose or frequent stools
• Abdominal painGastrointestinalUncommonPain or discomfort in the abdomen

Drug Interactions

• Gluten-containing medicationsModerate

Population Constraints

• Pediatric patientsAgeRelative
• Patients with severe renal or hepatic impairmentOrgan ImpairmentRelative
• Pregnant or breastfeeding womenReproductiveRelative

Regulatory Status

• European UnionInvestigationalNo EMA approval; investigated under EU clinical trial frameworks
• United StatesInvestigationalReceived FDA Fast Track designation for celiac disease. Phase 3 CeliAction trial did not meet primary endpoint. Not approved as of 2024.
• United KingdomInvestigationalNo MHRA approval; research/trial status only

Has received Fast Track designation from the FDA for celiac disease. Phase 3 trial (CeliAction study) did not meet its primary endpoint, but exploratory analyses showed benefit in certain subpopulations. As of 2024, not approved by FDA, EMA, or MHRA for any indication.

Evidence & Sources

No sources recorded yet.