Amylyx Pharmaceuticals presents new data on Avexitide for post-bariatric hypoglycemia

Amylyx Pharmaceuticals has represented analyses from the Phase 2 PREVENT and Phase 2b clinical trials of avexitide, an investigational, first-in-class glucagon-like peptide-1 (GLP-1) receptor antagonist for the treatment of post-bariatric hypoglycemia (PBH) at the Endocrine Society’s annual meeting (ENDO 2025).

In the Phase 2b trial, avexitide 90 mg once daily, the dose being evaluated in the pivotal Phase 3 LUCIDITY trial, led to a 64% least-squares (LS) mean reduction (p=0.0031) vs. baseline in the composite rate of Level 2 and Level 3 hypoglycaemic events in PBH, with more than half of the participants experiencing no events during the treatment period.

Consistent reductions in composite rate of Level 2 and Level 3 hypoglycaemic events also were seen with avexitide 45 mg twice daily studied in the Phase 2b trial and avexitide 30 mg twice daily and 60 mg once daily studied in the Phase 2 PREVENT trial. New pharmacokinetic (PK) and pharmacodynamic (PD) data were also presented demonstrating continuous pharmacologic activity of the 90 mg once daily dose regimen for a 24-hour period.

The population PK and PD analyses presented at ENDO 2025 demonstrated that avexitide 90 mg once daily maintained consistent GLP-1 receptor inhibition from morning to midnight and between doses. In vitro potency studies showed an IC₅₀ of approximately 20-30 nM (70-100 ng/mL), indicating robust target inhibition even in the presence of significant levels of GLP-1. PK modeling demonstrated that avexitide plasma levels exceeded IC₅₀ for a full 24-hour period.

LUCIDITY is a multi-centre, randomised, double-blind, placebo-controlled Phase 3 clinical trial evaluating the efficacy and safety of avexitide in approximately 75 participants with PBH following Roux-en-Y gastric bypass surgery. The FDA-agreed-upon primary endpoint of LUCIDITY is reduction in the composite of Level 2 and Level 3 hypoglycaemic events.

Avexitide is an investigational GLP-1) receptor antagonist that has been evaluated in five Phase 1 and Phase 2 clinical trials for PBH and has also been studied in congenital hyperinsulinism (HI). It is designed to bind to the GLP-1 receptor on pancreatic islet beta cells and inhibit the effect of GLP-1 to mitigate hypoglycemia by decreasing insulin secretion and stabilizing blood glucose levels. In PBH, excessive GLP-1 can lead to the hypersecretion of insulin and subsequent debilitating hypoglycaemic events. In two Phase 2 PBH clinical trials, avexitide demonstrated highly statistically significant reductions in hypoglycaemic events. These events can lead to autonomic and neuroglycopenic symptoms that can have a devastating impact on daily living.

“Post-bariatric hypoglycemia can profoundly disrupt daily life, requiring individuals to carefully manage meals, social interactions, and routines, often while living in fear of their next hypoglycaemic event. The new analysis presented at ENDO 2025 continues to support that avexitide may significantly reduce the frequency of these events,” said Dr Marilyn Tan, Principal Investigator of the LUCIDITY trial and Clinical Associate Professor at Stanford University.

LUCIDITY was informed by data from five PBH clinical trials of avexitide showing consistent, dose-dependent effects, including statistically significant and clinically meaningful reductions in hypoglycaemic events. Avexitide was generally well-tolerated, with a favourable safety profile replicated across clinical trials. Completion of recruitment for LUCIDITY is expected in 2025, with a data readout anticipated in the first half of 2026 and, if approved, commercial launch anticipated in 2027.