Amylyx Starts Phase 3 LUCIDITY Trial of Avexitide for Post-Bariatric Hypoglycemia

Amylyx Pharmaceuticals, Inc. has initiated the pivotal Phase 3 LUCIDITY trial, marking the dosing of the first participant. This trial focuses on evaluating avexitide, a novel glucagon-like peptide-1 (GLP-1) receptor antagonist, intended for managing post-bariatric hypoglycemia (PBH). Avexitide has already been recognized with several designations, including Breakthrough Therapy and Orphan Drug, by the U.S. Food and Drug Administration (FDA).

The LUCIDITY trial represents a significant step in Amylyx's journey to address the unmet needs of PBH patients. PBH is a serious condition affecting individuals who have undergone bariatric surgery, resulting in frequent, unpredictable low blood sugar events. These hypoglycemic episodes can severely impact daily life, causing symptoms such as cognitive impairment, unconsciousness, and seizures, thereby limiting the ability to live independently.

Camille L. Bedrosian, MD, Chief Medical Officer at Amylyx, underscored the importance of this trial as a milestone in avexitide's development. The company aims to provide an effective treatment option for those with PBH, building on data from five previous clinical trials that demonstrated avexitide's ability to significantly reduce hypoglycemic events in a consistent, dose-dependent manner.

The Phase 3 LUCIDITY trial, which adheres to FDA guidelines, is a multicenter, randomized, double-blind, placebo-controlled study involving approximately 75 participants who have previously undergone Roux-en-Y gastric bypass surgery. This trial will be conducted across about 20 sites in the United States. Participants are randomized in a 3:2 ratio to receive either a daily 90 mg dose of avexitide administered subcutaneously or a placebo. The trial encompasses a screening period of up to six weeks, including a three-week run-in period, followed by a 16-week double-blind treatment phase. Those who complete this phase will have the opportunity to join a 32-week open-label extension.

The primary goal of the LUCIDITY trial is to assess the efficacy of avexitide in reducing the composite of Level 2 and Level 3 hypoglycemic events by Week 16, as agreed with the FDA. Moreover, the trial will evaluate the safety and tolerability of the treatment. Amylyx plans to finalize recruitment by 2025 and anticipates releasing topline data in the first half of 2026.

Dr. Marilyn Tan, MD, FACE, a principal investigator for the LUCIDITY trial, highlighted the significant burden PBH places on individuals, making daily tasks, such as driving and social activities, challenging. Avexitide offers hope for a therapeutic option that could mitigate these burdens by reducing the frequency of hypoglycemic events.

Avexitide operates by binding to the GLP-1 receptor on pancreatic islet beta cells, thereby inhibiting the excessive insulin secretion triggered by GLP-1, which is a key factor in PBH. Previous trials have shown that avexitide can effectively stabilize blood glucose levels by decreasing insulin secretion.

Amylyx is committed to supporting the PBH community, recognizing the critical feedback from those living with PBH in shaping the LUCIDITY study design. With a targeted cash runway extending through 2026, Amylyx is poised to complete the LUCIDITY trial, aiming to bring a much-needed treatment to those affected by PBH.