Amylyx Pharmaceuticals has announced positive topline results from the phase 3 LUCIDITY trial evaluating avexitide in adults with post-bariatric hypoglycemia (PBH) following Roux-en-Y gastric bypass (RYGB) surgery.1
The trial met its primary endpoint as agreed with the US Food and Drug Administration (FDA), with the investigational glucagon-like peptide-1 (GLP-1) receptor antagonist reducing the composite rate of Level 2 and Level 3 hypoglycemic events by 55% compared with placebo (P = .000003). LUCIDITY also met all secondary endpoints, according to the company.1
“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,” Marilyn Tan, MD, clinical professor at the Stanford School of Medicine and principal investigator of the LUCIDITY trial, said in a statement. “Preventing even one Level 2 or Level 3 event is medically meaningful.”1
No FDA-approved therapies currently exist for PBH, a condition Amylyx estimates affects roughly 8% of patients following sleeve gastrectomy or RYGB surgery, or about 160,000 individuals in the United States. Avexitide already holds Breakthrough Therapy and Orphan Drug designations from the FDA. Amylyx plans to submit a new drug application (NDA) by the end of 2026.1
LUCIDITY (NCT06747468) is a 78-participant, multicenter, randomized, double-blind, placebo-controlled phase 3 trial conducted at 21 sites in the United States. Investigators randomized participants 3:2 to receive 90 mg of subcutaneous avexitide once daily or placebo. Design elements included:
- Up to a six-week screening period with a three-week run-in
- A 16-week double-blind treatment period
- A 32-week open-label extension1,2
Avexitide produced the 55% reduction in composite Level 2 and Level 3 hypoglycemic events through week 16, meeting the FDA-agreed primary endpoint. Level 2 events reflect clinically significant hypoglycemia requiring intervention, while Level 3 events involve severe cognitive impairment requiring assistance from another person. Amylyx reported the effect size as consistent with results from two earlier phase 2 trials of avexitide in PBH.1,2
Avexitide secondary endpoints and safety in LUCIDITY
LUCIDITY met all secondary endpoints, with consistent, statistically significant, and clinically meaningful reductions across three additional measures compared with placebo. These included Level 2 events by self-monitoring of blood glucose (SMBG), Level 2 events by continuous glucose monitoring (CGM), and independently adjudicated Level 3 events, according to Amylyx.1,2
The company described avexitide as generally well tolerated through the double-blind treatment period, with a safety profile consistent across all completed PBH trials to date. Most adverse events were mild to moderate, and no serious adverse events were considered related to avexitide. The most common adverse events were diarrhea, injection site erythema, and injection site bruising.1
Body weight did not change in either treatment arm over the 16-week double-blind period, according to the company. Amylyx noted the safety findings align with prior avexitide trials in PBH, supporting the agent's overall tolerability profile as it moves toward regulatory submission.1
Amylyx plans to present LUCIDITY data at an upcoming medical meeting and is preparing for a potential commercial launch of avexitide in 2027, if approved. The LUCIDITY open-label extension and the avexitide expanded access program, launched in May 2026, remain ongoing, and avexitide is also under investigation for congenital hyperinsulinism.1
References
A study of avexitide in post-bariatric hypoglycemia (LUCIDITY). ClinicalTrials.gov identifier: NCT06747468. Accessed August 18, 2026. https://clinicaltrials.gov/study/NCT06747468
