An Endocrine News roundup of the week’s pharmaceutical news, breakthroughs, and general information. *
First Participant Dosed in Pivotal Phase 3 LUCIDITY Trial of Avexitide in Post-Bariatric Hypoglycemia
On April 30, Amylyx Pharmaceuticals, Inc. announced that the first participant has been dosed in the pivotal Phase 3 LUCIDITY clinical trial of avexitide, an investigational, first-in-class glucagon-like peptide-1 (GLP-1) receptor antagonist, for the treatment of post-bariatric hypoglycemia (PBH).
“The first participant dosed in our Phase 3 LUCIDITY trial marks a milestone in the clinical development of avexitide, moving us one step closer toward potentially bringing this investigational therapy to people living with post-bariatric hypoglycemia,” said Endocrine Society member Camille L. Bedrosian, MD, chief medical officer at Amylyx. “With robust data generated to date from five previous clinical trials in PBH, we are excited about the potential for avexitide to address the persistent, recurrent, and debilitating hypoglycemic events associated with PBH. As we work toward bringing a much-needed treatment to the PBH community, we want to thank those who are living with PBH who provided invaluable feedback on the LUCIDITY study design. Additionally, we are grateful for the collaboration of the avexitide clinical trial investigators.”
“Post-bariatric hypoglycemia places a tremendous burden on individuals, with frequent and unpredictable hypoglycemic events that can cause severe symptoms such as impaired cognition, loss of consciousness, and seizures,” said Endocrine Society member Marilyn Tan, MD, principal investigator of the LUCIDITY clinical trial and clinical associate professor of medicine at Stanford University School of Medicine. “These events disrupt independent living, often making it difficult to drive, work, live alone, or engage in social activities. Avexitide has the potential to significantly reduce hypoglycemic events, offering a much-needed therapeutic option for those living with PBH.”
LUCIDITY (NCT06747468) is a multicenter, randomized, double-blind, placebo-controlled Phase 3 clinical trial evaluating the efficacy and safety of avexitide in approximately 75 participants with PBH following Roux-en-Y gastric bypass (RYGB) surgery, across approximately 20 U.S. sites. The U.S. Food and Drug Administration (FDA)-agreed-upon primary endpoint of LUCIDITY is reduction in the composite of Level 2 and Level 3 hypoglycemic events through Week 16. The trial includes similar inclusion and exclusion criteria to previous Phase 2 trials of avexitide in PBH. Safety and tolerability will also be evaluated.
Participants will be randomized 3:2 to receive either 90 mg of avexitide subcutaneously once daily or placebo. The trial includes an up to six-week screening period, including a three-week run-in period, and a 16-week double-blind treatment period. Participants who complete the double-blind period of the study will be eligible to enter an open-label extension (OLE) period with a duration of 32 weeks. Amylyx presented the design of LUCIDITY in December 2024, and the poster is available on the “Publications” page of the Amylyx website.
LUCIDITY was informed by data from five PBH clinical trials of avexitide showing consistent, dose-dependent effects, including statistically significant reductions in hypoglycemic events. Avexitide was generally well tolerated, with a favorable safety profile replicated across clinical trials.
The Company continues to expect cash runway through the end of 2026, which will support the completion of recruitment for the pivotal Phase 3 LUCIDITY clinical trial of avexitide in PBH expected in 2025, with a data readout anticipated in the first half of 2026.
About Avexitide
Avexitide is an investigational, first-in-class glucagon-like peptide-1 (GLP-1) receptor antagonist that has been evaluated in five Phase 1 and Phase 2 clinical trials for post-bariatric hypoglycemia (PBH) and has also been studied in congenital hyperinsulinism (HI). The U.S. Food and Drug Administration (FDA) has granted avexitide Breakthrough Therapy Designation for both indications, Rare Pediatric Disease Designation in congenital HI, and Orphan Drug Designation for the treatment of hyperinsulinemic hypoglycemia (which includes PBH and congenital HI). Avexitide is designed to bind to the GLP-1 receptor on pancreatic islet beta cells and inhibit the effect of GLP-1 to mitigate hypoglycemia by decreasing insulin secretion and stabilizing blood glucose levels. In PBH, excessive GLP-1 can lead to the hypersecretion of insulin and subsequent debilitating hypoglycemic events. In two Phase 2 PBH clinical trials, avexitide demonstrated highly statistically significant reductions in hypoglycemic events. These events can lead to autonomic and neuroglycopenic symptoms that can have a devastating impact on daily living.
About Post-Bariatric Hypoglycemia (PBH)
Post-bariatric hypoglycemia (PBH) is a condition that affects approximately 8% of people in the U.S., or approximately 160,000 people, who have undergone the two most common types of bariatric surgery, which include sleeve gastrectomy and Roux-en-Y gastric bypass (RYGB). PBH is thought to be caused by an excessive glucagon-like peptide-1 (GLP-1) response leading to hypoglycemia and impaired quality of life. PBH can cause debilitating hypoglycemic events associated with inadequate supply of glucose to the brain, known as neuroglycopenia. Clinical manifestations can include impaired cognition, loss of consciousness, and seizures. PBH is also associated with a high degree of disability that can result in major disruptions to independent living. There are no approved therapies for PBH.
About the LUCIDITY Trial
LUCIDITY (NCT06747468) is an approximately 75-participant, multicenter, randomized, double-blind, placebo-controlled Phase 3 clinical trial evaluating the efficacy and safety of avexitide in participants with PBH following Roux-en-Y gastric bypass (RYGB) surgery. The Phase 3 trial will be conducted at approximately 20 sites in the U.S. Participants will be randomized 3:2 to receive either 90 mg of avexitide subcutaneously once daily or placebo. The trial includes an up to six-week screening period, including a three-week run-in period, and a 16-week double-blind treatment period. Participants who complete the double-blind period will be eligible to enter an open-label extension (OLE) period with a duration of 32 weeks. The primary efficacy objective of LUCIDITY will evaluate the FDA-agreed upon primary outcome of reduction in the composite of Level 2 and Level 3 hypoglycemic events through Week 16. Safety and tolerability will also be evaluated.
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