CAMBRIDGE, Mass., August 18, 2026
Amylyx Pharmaceuticals, Inc. announced positive topline results from the Phase 3 LUCIDITY clinical trial evaluating avexitide in adults with post-bariatric hypoglycemia (PBH) following Roux-en-Y gastric bypass surgery. The results represent an important clinical development for a condition for which there are currently no FDA-approved therapies. Avexitide is an investigational, first-in-class GLP-1 receptor antagonist designed to address the excessive GLP-1-driven insulin response believed to contribute to recurrent hypoglycemia in PBH. The LUCIDITY study met its FDA-agreed primary endpoint, while Amylyx said preparations are underway for a potential New Drug Application (NDA) submission by the end of 2026.
LUCIDITY Advances Potential PBH Treatment
The 78-participant Phase 3 LUCIDITY trial was designed to evaluate the efficacy and safety of once-daily subcutaneous avexitide compared with placebo. Participants were randomized in a 3:2 ratio to receive 90 mg avexitide or placebo during the 16-week double-blind treatment period. The study was conducted across 21 sites in the United States and includes a subsequent 32-week open-label extension. PBH can cause recurrent and potentially debilitating drops in blood glucose following bariatric surgery, with more severe episodes capable of causing confusion, cognitive impairment, loss of consciousness and seizures. The condition is believed to involve an exaggerated GLP-1 response following food intake, which can trigger excessive insulin secretion and subsequent hypoglycemia. By targeting the GLP-1 receptor, avexitide is designed to reduce inappropriate insulin secretion and stabilize blood glucose levels, providing a targeted approach to an area of significant unmet medical need.
Avexitide Shows Broad Clinical Activity in Phase 3
The LUCIDITY trial achieved its primary endpoint by demonstrating a 55% reduction in the composite rate of Level 2 and Level 3 hypoglycemic events compared with placebo through Week 16, with a highly statistically significant p-value of 0.000003. Importantly, the clinical benefit was not limited to the primary analysis. Amylyx reported that all secondary endpoints were met, showing consistent and statistically significant reductions in Level 2 hypoglycemic events measured through self-monitoring of blood glucose and continuous glucose monitoring, as well as independently adjudicated Level 3 events. Avexitide was also generally well tolerated, with a safety profile consistent with previous PBH clinical studies. Most adverse events were mild to moderate, while reported events included diarrhea, injection-site erythema and injection-site bruising. No serious adverse events related to avexitide were reported during the double-blind period, and no changes in body weight were observed between the treatment groups..
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Amylyx Prepares FDA Filing for Avexitide
Following the positive Phase 3 results, Amylyx Pharmaceuticals plans to submit an NDA to the FDA by the end of 2026, potentially positioning avexitide for regulatory review as a treatment for PBH. The investigational therapy has already received FDA Breakthrough Therapy Designation for PBH, along with Orphan Drug Designation for hyperinsulinemic hypoglycemia. The company is continuing the 32-week open-label extension of LUCIDITY and its expanded access program, which began in May 2026. Amylyx also plans to present detailed LUCIDITY data at an upcoming medical meeting. If the regulatory process progresses successfully, the company is preparing for a potential commercial launch in 2027. The topline Phase 3 findings build on results from five previous clinical trials of avexitide in PBH and strengthen the company’s development strategy around endocrine disorders with substantial unmet treatment needs.
Source:Amylyx Pharmaceuticals, press relese
