Amylyx Pharmaceuticals announced positive topline results from the Phase 3 LUCIDITY trial evaluating avexitide, an investigational first-in-class GLP-1 receptor antagonist, in adults with post-bariatric hypoglycemia (PBH) after Roux-en-Y gastric bypass (RYGB). The company reported that LUCIDITY met its FDA-agreed primary endpoint and all secondary endpoints, with a large and statistically significant reduction in clinically meaningful hypoglycemic events. Company leadership and trial investigators described the results as an important milestone toward the potential first approved therapy for PBH.
LUCIDITY was a multicenter, randomized, double-blind, placebo-controlled Phase 3 clinical trial. The study enrolled 78 adult participants with PBH following RYGB surgery. Participants were randomized in a 3:2 ratio to receive either 90 mg avexitide given subcutaneously once daily or placebo.
The double-blind evaluation covered a 16-week period during which primary and secondary efficacy endpoints were assessed. After the double-blind portion, a 32-week open-label extension (OLE) remains ongoing. Amylyx also operates an avexitide expanded access program (EAP), which launched in May and continues to provide access for eligible individuals.
LUCIDITY met its primary endpoint, demonstrating a 55% reduction in the composite rate of Level 2 and Level 3 hypoglycemic events compared with placebo through Week 16 (reported p=0.000003). The trial also met all prespecified secondary endpoints, showing consistent and statistically significant reductions in:
Investigators characterized these reductions as both highly statistically significant and clinically meaningful. The source notes that Level 2 and Level 3 events can be medical emergencies associated with cognitive or physical impairment, loss of consciousness, seizures, and need for assistance, and that preventing even a single such event is medically meaningful for patients with PBH.
During the 16-week double-blind study period, avexitide was generally well tolerated and demonstrated a safety profile consistent with prior PBH clinical trials. The majority of adverse events were reported as mild to moderate in severity.
No serious adverse events were attributed to avexitide in the double-blind period according to the company. The most commonly reported adverse events in LUCIDITY were diarrhea, injection site erythema, and injection site bruising. No change in body weight was observed in either the avexitide or placebo groups over the 16-week double-blind period.
Amylyx stated plans to submit a New Drug Application (NDA) to the U.S. Food and Drug Administration by the end of 2026. Avexitide has previously received FDA Breakthrough Therapy Designation for PBH.
The LUCIDITY 32-week open-label extension remains ongoing, and the company continues to operate the expanded access program that began in May. Amylyx indicated preparations for potential commercial launch in 2027 if regulatory approval is obtained and plans to present LUCIDITY data at an upcoming medical meeting.
Endocrine Society member Marilyn Tan, MD, principal investigator of the LUCIDITY trial and clinical professor at Stanford School of Medicine, emphasized the clinical importance of reducing Level 2 and Level 3 hypoglycemic events, noting their potential to cause significant cognitive or physical impairment and other severe outcomes. Dr. Tan stated that preventing even one such event is medically meaningful and expressed excitement about the LUCIDITY findings.
Camille L. Bedrosian, MD, chief medical officer at Amylyx, described the results as a major milestone that could address a critical treatment gap for the PBH community and cited positive data from five prior avexitide PBH trials as supporting evidence. Company co-CEOs Justin Klee and Joshua Cohen expressed gratitude to trial participants and to the PBH community and reiterated the company’s readiness activities for an NDA submission and potential commercial launch.
Note: This summary is based solely on the information reported in the Endocrine News article. Details such as full statistical analyses, individual subgroup results, or complete safety tables were not reported in the source and are therefore not included here.