Avexitide, a first-in-class glucagon-like peptide-1 (GLP-1) receptor antagonist, met the primary endpoint of the Phase III LUCIDITY trial in post-bariatric hypoglycemia (PBH), delivering a 55% reduction in composite Level 2 and Level 3 hypoglycemic events versus placebo (p=0.000003), according to topline results released August 18. Cambridge, Massachusetts-based Amylyx Pharmaceuticals (Nasdaq: AMLX) said it plans to submit a New Drug Application (NDA) to the FDA by year-end, targeting a 2027 commercial launch if approved.
PBH is estimated to affect approximately 160,000 people in the US who have undergone Roux-en-Y gastric bypass (RYGB) surgery, and no FDA-approved treatment currently exists. Management of the condition relies entirely on off-label agents — including acarbose, diazoxide, and octreotide — none of which is mechanistically targeted to the GLP-1-driven pathophysiology specific to PBH. Avexitide competitively binds the GLP-1 receptor on pancreatic beta cells, blocking the exaggerated postprandial GLP-1 response that drives excessive insulin secretion and recurrent hypoglycemia in these patients.
LUCIDITY enrolled 78 adults with PBH following RYGB, randomized 3:2 to 90 mg avexitide subcutaneously once daily or placebo across 21 US sites. The 16-week double-blind period met all four prespecified endpoints: the primary composite of Level 2 and Level 3 events, and three secondary endpoints covering Level 2 events by self-monitoring of blood glucose (SMBG), Level 2 events by continuous glucose monitoring (CGM), and independently adjudicated Level 3 events. Amylyx described all secondary reductions as highly statistically significant, though granular figures for those endpoints were not disclosed and will be presented at an upcoming medical meeting. No body weight changes were observed in either group, and there were no serious adverse events related to avexitide; the most common adverse events were diarrhea, injection site erythema, and injection site bruising.
The LUCIDITY result builds on a consistent body of earlier evidence. Phase II and Phase IIb data presented at ENDO 2025 showed avexitide 90 mg once daily — the same dose evaluated in LUCIDITY — achieved a 64% least-squares mean reduction in the composite of Level 2 and Level 3 events versus baseline (p=0.0031) in the Phase IIb cohort, with more than half of participants experiencing no events during the treatment period. The FDA had previously granted avexitide Breakthrough Therapy Designation for PBH, as well as Orphan Drug Designation for hyperinsulinemic hypoglycemia.
Avexitide came to Amylyx through its 2024 acquisition of the drug and other assets from Eiger BioPharmaceuticals for approximately USD 35 million through a bankruptcy sale. Eiger had advanced avexitide through Phase II development in PBH before financial difficulties led the company to file for Chapter 11 protection in 2024. Amylyx subsequently made avexitide its lead clinical program, taking the asset into the pivotal LUCIDITY study that has now delivered positive Phase III results.