LUCIDITY: Avexitide reduce level 2 and 3 hypoglycaemic events by 55%

Amylyx Pharmaceuticals has announced positive topline results from LUCIDITY, a 78-participant, multi-centre, randomised, double-blind, placebo-controlled Phase 3 clinical trial evaluating the efficacy and safety of avexitide, an investigational, first-in-class glucagon-like peptide-1 (GLP-1) receptor antagonist, in participants with post-bariatric hypoglycemia (PBH) following Roux-en-Y gastric bypass (RYGB) surgery.

LUCIDITY met the FDA-agreed-upon primary endpoint demonstrating a 55% reduction in the composite rate of Level 2 and Level 3 hypoglycaemic events compared to placebo (p=0.000003). In addition, LUCIDITY met all secondary endpoints demonstrating consistent, highly statistically significant, and clinically meaningful reductions in Level 2 hypoglycaemic events by self-monitoring of blood glucose (SMBG), Level 2 hypoglycaemic events by continuous glucose monitoring (CGM), and Level 3 hypoglycaemic events.

“PBH is a chronic metabolic condition that causes recurrent and often debilitating hypoglycemia, which has a significant negative impact on patients’ safety and quality of life,” said Dr Marilyn Tan, Principal Investigator of the LUCIDITY clinical trial and Clinical Professor at the Stanford School of Medicine. “Level 2 and Level 3 hypoglycaemic events can be medical emergencies that result in significant cognitive or physical impairment, loss of consciousness, seizures, and the need for assistance from others, underscoring the need for an FDA-approved treatment option. Preventing even one Level 2 or Level 3 event is medically meaningful. I am excited by the LUCIDITY results announced today and the potential to have the first treatment for patients with PBH.”

The Phase 3 LUCIDITY trial enrolled 78 adult participants with PBH following RYGB surgery. Participants were randomised 3:2 to receive either 90 mg avexitide subcutaneously once daily or placebo. Avexitide was generally well-tolerated through the double-blind study period with a consistent and favourable safety profile replicated across all PBH clinical trials completed to date. The majority of adverse events in LUCIDITY were mild to moderate, and there were no serious adverse events related to avexitide treatment. The most common adverse events were diarrhoea, injection site erythema and injection site bruising. There were no changes in body weight observed in either the avexitide or placebo groups over the 16-week, double-blind period of the LUCIDITY trial.

Amylyx plans to submit a New Drug Application (NDA) to the FDA by the end of 2026. The FDA previously granted avexitide Breakthrough Therapy Designation for PBH. LUCIDITY’s 32-week open label extension (OLE) remains ongoing. The avexitide expanded access program (EAP) also remains ongoing.

“Today’s data represent an exciting outcome for the PBH community and mark an important milestone as we work toward what could be the first approved treatment option for this condition,” said Justin Klee and Joshua Cohen, Co-CEOs of Amylyx. “Our NDA submission readiness is well underway, and we continue to advance our preparations for a potential commercial launch of avexitide in 2027, if approved.”