Amylyx Pharmaceuticals (NASDAQ:AMLX) said its Phase III LUCIDITY trial of avexitide met its primary endpoint, reducing the composite rate of clinically significant hypoglycemic events by 55% versus placebo in adults with post-bariatric hypoglycemia following Roux-en-Y gastric bypass surgery.
The randomized, double-blind, placebo-controlled trial enrolled 78 participants, who were assigned in a three-to-two ratio to receive 90 milligrams of avexitide once daily or placebo over 16 weeks. More than 90% of participants completed the double-blind treatment period, according to the company, and all eligible participants entered an ongoing open-label extension.
Primary and Secondary Endpoints Met
Camille Bedrosian, Amylyx’s chief medical officer, said LUCIDITY achieved its FDA-agreed primary endpoint with a 55% reduction in the composite rate of Level 2 and Level 3 hypoglycemic events compared with placebo, with a p-value of 0.000003.
Level 2 hypoglycemia was defined as a glucose measurement below 54 milligrams per deciliter. Level 3 events were defined as episodes involving cognitive or physical impairment requiring assistance from another person.
The study also met all prespecified secondary endpoints, including reductions in Level 2 events measured through self-monitoring of blood glucose and continuous glucose monitoring, as well as reductions in Level 3 events. Amylyx did not disclose detailed absolute event rates, placebo response figures or the proportion of patients who were event-free, saying it intends to reserve further details for scientific presentations and publications.
Bedrosian said the results were consistent with the company’s prior Phase II PREVENT study, which also showed a 55% reduction in the composite endpoint relative to placebo. She characterized LUCIDITY as the sixth avexitide study to produce statistically significant results in PBH and the largest and longest study of the drug in the condition to date.
Safety Profile and Patient Impact
Avexitide was generally well tolerated during the double-blind portion of the trial, Amylyx said. Most adverse events were mild or moderate, and there were no serious adverse events considered related to treatment. The most common adverse events were diarrhea, injection-site redness and injection-site bruising. The company also reported no observed change in body weight in either treatment group during the 16-week period.
Marilyn Tan, principal investigator for LUCIDITY and a clinical professor of medicine at Stanford University School of Medicine, said PBH can result in recurrent and unpredictable glucose crashes that may cause cognitive impairment, loss of consciousness and seizures. The condition can affect patients’ ability to work, drive, care for family members and live independently, she said.
Tan said published literature suggests PBH affects about 5% of people who undergo sleeve gastrectomy and 12% of those who undergo Roux-en-Y gastric bypass. Amylyx estimates that approximately 160,000 people in the U.S. require medical management for the condition, including roughly 120,000 whose PBH followed Roux-en-Y gastric bypass.
Current management consists primarily of medical nutrition therapy and off-label medications, according to the speakers. Tan said acarbose is commonly used off label but estimated that fewer than 5% of her patients are reasonably controlled with acarbose alone.
Regulatory and Commercial Plans
Amylyx said avexitide has received FDA breakthrough therapy designation and that it plans to submit a New Drug Application by the end of the year. The company said it intends to seek priority review and plans to submit the full application at once rather than use a rolling submission process.
Josh Cohen, co-chief executive officer, said Amylyx has been preparing the NDA throughout the year and expects the Phase III data and associated documentation to be the final major component of the filing. The company is preparing for a potential U.S. launch in 2027 if avexitide receives approval.
The Phase III trial was limited to patients whose PBH followed Roux-en-Y gastric bypass surgery. However, Tan noted that an earlier Phase IIb trial included patients with other surgical histories, including vertical sleeve gastrectomy and gastrectomy, and that those subgroups appeared to show similarly robust reductions in Level 2 and Level 3 events. Amylyx said it believes PBH may respond to treatment regardless of the surgery that preceded it, though the eventual FDA label remains to be determined.
The company also discussed AMX0318, a longer-acting GLP-1 receptor antagonist being developed as part of its broader PBH franchise. Amylyx said the candidate is in IND-enabling studies and that it expects to submit an investigational new drug application for AMX0318 in 2027.
Amylyx reported having more than $250 million in cash at the end of the second quarter and said it is expanding medical-affairs and commercial capabilities while conducting disease education efforts for healthcare providers and the PBH community.
About Amylyx Pharmaceuticals (NASDAQ:AMLX)
Amylyx Pharmaceuticals, Inc is a biopharmaceutical company dedicated to developing treatments for rare and debilitating neurological diseases. Founded in 2013 and headquartered in Cambridge, Massachusetts, the company focuses on leveraging novel approaches to target cellular pathways implicated in neurodegeneration. Amylyx’s research platform centers on small-molecule therapies designed to protect neurons and support cellular health in patients with conditions that currently have limited or no disease-modifying treatment options.
The company’s lead product, AMX0035, is marketed under the trade name Relyvrio following U.S.
