GLP-1 Avexitide Continues to Show Promise in Reducing Hypoglycemia After Bariatric Surgery in Phase II Trials

Amylyx has announced new exploratory analyses from two Phase II 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). These data were presented at the Endocrine Society’s annual meeting (ENDO 2025).¹

New Phase II results demonstrate significant reductions in severe hypoglycemia

In a Phase IIb study (NCT04652479), avexitide at a dose of 90 mg once daily demonstrated a 64% least-squares mean reduction (p=0.0031) versus baseline in the composite rate of Level 2 and Level 3 hypoglycemic events in PBH. Further, more than half of the participants did not experience any events during the treatment period.

This trial also evaluated avexitide at 45 mg twice daily, which showed consistent reductions in composite rate of Level 2 and Level 3 hypoglycemic events.

PREVENT trial supports consistency across lower doses

Meanwhile, new data from the Phase II PREVENT trial (NCT03373435) also showed consistent reductions in composite rate of Level 2 and Level 3 hypoglycemic events, but at doses of 30 mg twice daily and 60 mg once daily.

LUCIDITY Phase III trial to build on promising earlier data

In addition to the new Phase II analyses of avexitide, Amylyx provided an update on its Phase III LUCIDITY trial (NCT06747468) of avexitide. According to the company, LUCIDITY was informed by positive, consistent data stemming from five PBH studies. Recruitment is expected to be completed this year with the first data readout anticipated in the first half of 2026. If avexitide is approved, Amylyx expects commercial launch in 2027.

In a press release, Marilyn Tan, MD, FACE, principal investigator of the LUCIDITY trial and clinical associate professor at Stanford University, said: “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 hypoglycemic event. The new analysis presented at ENDO 2025 continues to support that avexitide may significantly reduce the frequency of these events.”

Study design highlights for LUCIDITY trial

• LUCIDITY is a randomized, double-blind, placebo-controlled trial evaluating avexitide in patients with PBH after Roux-en-Y gastric bypass surgery.
• The study will enroll approximately 75 participants across 20 US sites.
• Participants will be randomized 3:2 to receive either 90 mg avexitide subcutaneously once daily or placebo.
• The trial includes a screening period of up to six weeks, which incorporates a three-week run-in, followed by a 16-week double-blind treatment phase.
• Those completing the double-blind phase may continue in a 32-week open-label extension period.
• The primary efficacy goal is to measure the reduction in Level 2 and Level 3 hypoglycemic events through 16 weeks, per FDA agreement.
• Additional assessments will include safety and tolerability of avexitide.

Earlier Phase II results demonstrated strong efficacy and safety signals

In July 2024, Amylyx acquired avexitide from Eiger BioPharmaceuticals. Additionally, the treatment received Breakthrough Therapy Designation by the FDA for a number of indications including PBH and congenital hyperinsulinism. At the time of the announcement, Amylyx shared earlier readouts from the Phase II studies of avexitide.²

In the Phase II PREVENT study:

• Avexitide 30 mg and 60 mg twice daily increased mean glucose nadir by 21% and 26%, respectively, compared to placebo.
• Peak insulin levels dropped by 23% in the 30 mg group and 21% in the 60 mg group, leading to 50% and 75% fewer participants needing rescue therapy during mixed meal tolerance tests.
• The treatment also resulted in notable reductions in hypoglycemia rates across all severity levels (Levels 1, 2, and 3).

In the Phase IIb trial of avexitide:

• The treatment hit its primary endpoint, showing a reduction in daytime Level 2 hypoglycemia events (glucose <54 mg/dL) as measured by continuous glucose monitoring.
• In the 45 mg twice-daily group, hypoglycemia rates decreased by:
  • 54% at Level 1
  • 57% at Level 2
  • 68% at Level 3 (severe events)
• In the 90 mg once-daily group, reductions were:
  • 68% at Level 1
  • 53% at Level 2
  • 66% at Level 3

References

1. Amylyx Pharmaceuticals Presents New Exploratory Analyses from Phase 2 and Phase 2b Clinical Trials of Avexitide in Post-Bariatric Hypoglycemia at ENDO 2025. News release. Amylyx Pharmaceuticals. July 13, 2025. Accessed July 15, 2025. https://www.businesswire.com/news/home/20250713408050/en/Amylyx-Pharmaceuticals-Presents-New-Exploratory-Analyses-from-Phase-2-and-Phase-2b-Clinical-Trials-of-Avexitide-in-Post-Bariatric-Hypoglycemia-at-ENDO-2025

2. Amylyx Pharmaceuticals Acquires Phase III-Ready GLP-1 Receptor Agonist Avexitide for Hyperinsulinemic Hypoglycemia from Eiger BioPharmaceuticals. Pharmaceutical Executive. July 12, 2024. Accessed July 15, 2025. https://www.pharmexec.com/view/amylyx-pharmaceuticals-acquires-phase-iii-ready-glp-1-receptor-agonist-avexitide-hyperinsulinemic-hypoglycemia-eiger-biopharmaceuticals