CAMBRIDGE, Mass. — Amylyx Pharmaceuticals, Inc. said its Phase 3 LUCIDITY trial of avexitide met its primary endpoint and all secondary endpoints in patients with post-bariatric hypoglycemia following Roux-en-Y gastric bypass surgery.
The 78-patient, multicenter, randomized, double-blind, placebo-controlled study evaluated avexitide, an investigational glucagon-like peptide-1 receptor antagonist. Amylyx said the drug produced a 55% reduction in the composite rate of Level 2 and Level 3 hypoglycemic events compared with placebo through Week 16, meeting the primary endpoint agreed upon with the U.S. Food and Drug Administration.
The result was highly statistically significant, with a p-value of 0.000003.
LUCIDITY also met all secondary endpoints, demonstrating reductions in Level 2 hypoglycemic events measured by self-monitoring of blood glucose, Level 2 events measured by continuous glucose monitoring and independently adjudicated Level 3 hypoglycemic 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 Marilyn Tan, M.D., FACE, Principal Investigator of the LUCIDITY clinical trial and Clinical Professor at Stanford School of Medicine. “Level 2 and Level 3 hypoglycemic 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.”
Participants in LUCIDITY were randomized 3:2 to receive either 90 mg of avexitide subcutaneously once daily or placebo.
Amylyx said avexitide was generally well tolerated during the double-blind portion of the study. Most adverse events were mild to moderate, and no serious adverse events related to avexitide treatment were reported. The most common adverse events were diarrhea, injection-site erythema and injection-site bruising.
No changes in body weight were observed in either the avexitide or placebo groups during the 16-week double-blind treatment period.
“Today’s results are a major milestone that demonstrate avexitide’s potential to address a critical treatment gap for the PBH community and represent a meaningful step forward for people living with this condition,” said Camille L. Bedrosian, M.D., Chief Medical Officer at Amylyx.
Amylyx said the Phase 3 findings build on positive results from five previous clinical trials of avexitide in post-bariatric hypoglycemia.
The company plans to submit a New Drug Application for avexitide to the FDA by the end of 2026. The FDA has previously granted the therapy Breakthrough Therapy Designation and Orphan Drug Designation for post-bariatric hypoglycemia.
Amylyx is also continuing a 32-week open-label extension of the LUCIDITY trial and an expanded access program for eligible patients. The company plans to present detailed LUCIDITY data at an upcoming medical meeting.
“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,” said Justin Klee and Joshua Cohen, Co-CEOs of Amylyx.
