Amylyx completes LUCIDITY Clinical Trial enrolment assessing avexitide for post-bariatric hypoglycemia

The last participant has been randomised and dosed in Amylyx Pharmaceuticals’ pivotal Phase 3 LUCIDITY clinical trial of avexitide, an investigational, first-in-class glucagon-like peptide-1 (GLP-1) receptor antagonist with an FDA Breakthrough Therapy Designation in post-bariatric hypoglycemia (PBH).

LUCIDITY is a 16-week, multicentre, randomised, double-blind, placebo-controlled trial evaluating the efficacy and safety of avexitide in adults with PBH following Roux-en-Y gastric bypass (RYGB) surgery. The trial has enrolled 78 participants, with topline data readout anticipated in Q3 2026. If approved, commercial launch of avexitide is anticipated in 2027.

The Phase 3 trial is being conducted at 21 sites in the US. Participants were randomised 3:2 to receive either 90 mg of avexitide subcutaneously once daily or placebo. The trial includes an up to six-week screening period, including a three-week run-in period, a 16-week double-blind treatment period, and an open-label extension (OLE) period with a duration of 32 weeks. The primary efficacy objective of LUCIDITY is to evaluate the FDA-agreed upon primary outcome of reduction in the composite of Level 2 and Level 3 hypoglycaemic events through Week 16. Safety and tolerability will also be evaluated.

“Today, living with PBH means living with constant and unpredictable hypoglycaemic events, which studies have shown are driven by an exaggerated GLP-1 response. These events can lead to severe medical consequences, such as seizures, loss of consciousness, emergency department visits, hospitalisation and long-term impacts, including cognitive dysfunction. The significant burden of this chronic metabolic condition can strip away independence, forcing many of my patients to withdraw from their work and social lives,” said Dr Marilyn Tan, Principal Investigator of the LUCIDITY clinical trial and Clinical Professor of Medicine at the Stanford School of Medicine. “Preventing even a single event could meaningfully improve someone’s quality of life and there is an urgent need for medicine to treat this devastating condition.”

Avexitide is an investigational, first-in-class glucagon-like peptide-1 (GLP-1) receptor antagonist that has been evaluated in five Phase 1 and Phase 2 clinical trials for post-bariatric hypoglycemia (PBH) and has also been studied in congenital hyperinsulinism (HI). The FDA has granted avexitide Breakthrough Therapy Designation for both indications, Rare Pediatric Disease Designation in congenital HI, and Orphan Drug Designation for the treatment of hyperinsulinaemic hypoglycemia (which includes PBH and congenital HI).

In PBH, an exaggerated GLP-1 response leads to excessive insulin secretion, resulting in recurrent hypoglycaemic events. Avexitide is a competitive GLP-1 receptor antagonist designed to bind to the GLP-1 receptor on pancreatic islet beta cells and inhibit the exaggerated GLP-1-driven insulin response characteristic of PBH, reducing inappropriate insulin secretion and stabilizing blood glucose levels. In two Phase 2 PBH clinical trials, avexitide demonstrated highly statistically significant reductions in hypoglycaemic events.