Livoletide

Summary

Livoletide (AZP-531) is an acylated analogue of unacylated ghrelin being investigated primarily for the treatment of hyperphagia and obesity associated with Prader-Willi syndrome (PWS). It has shown signals of reducing food-seeking behavior and improving metabolic outcomes in early clinical trials. Developed by Aeterna Zentaris (formerly AZP Pharma).

Mechanism of Action

Livoletide is an analogue of unacylated ghrelin (UAG) that acts as a functional antagonist of acylated ghrelin (AG) signaling. It does not activate the classical ghrelin receptor (GHSR1a) but modulates downstream pathways to reduce hyperphagia, improve metabolic parameters, and potentially decrease fat mass. The exact receptor target mediating its effects remains under investigation.

Routes of Administration

Goals & Uses

• Body weight / fat mass reductionMetabolicLow
• Reduction of hyperphagia in Prader-Willi syndromeSymptom ManagementModerate
• Behavioral improvement in PWSNeurobehavioralModerate
• Improvement of glycemic parametersMetabolicLow

Contraindications

• Known hypersensitivity to livoletide or excipientsAllergy/HypersensitivityHigh

Adverse Effects

• Injection site reactionsLocalCommon
• HeadacheNeurologicUncommonPain in the head or upper neck
• NauseaGastrointestinalUncommonFeeling of sickness or urge to vomit
• FatigueGeneralUncommonLow energy or tiredness

Drug Interactions

• Growth hormone therapyLow
• Insulin / antidiabetic agentsLow

Population Constraints

• Severe renal or hepatic impairmentOrgan FunctionRelative
• PregnancyReproductive SafetyRelative
• Pediatric patients (under 12 years)AgeRelative

Regulatory Status

• European UnionInvestigationalEMA Orphan Drug Designation granted for Prader-Willi syndrome. No marketing authorization approved.
• United StatesInvestigationalFDA Orphan Drug Designation granted for Prader-Willi syndrome. No approved marketing authorization as of knowledge cutoff.

Livoletide has received Orphan Drug Designation from both the FDA and EMA for Prader-Willi syndrome. It has not received marketing approval in any jurisdiction as of the knowledge cutoff. Phase 2 clinical trials have been conducted.

Evidence & Sources

No sources recorded yet.