An Endocrine News roundup of the week’s pharmaceutical news, breakthroughs, and general information. *
Amylyx Pharmaceuticals Announces Positive Topline Results from Phase 3 LUCIDITY Clinical Trial of Avexitide in Post-Bariatric Hypoglycemia
On August 18, Amylyx Pharmaceuticals, Inc., announced positive topline results from LUCIDITY, a 78-participant, multicenter, randomized, double-blind, placebo-controlled Phase 3 clinical trial evaluating the efficacy and safety of avexitide, an investigational, first-in-class glucagon-like peptide-1 (GLP-1) receptor antagonist, in participants with post-bariatric hypoglycemia (PBH) following Roux-en-Y gastric bypass (RYGB) surgery.
LUCIDITY met the FDA-agreed-upon primary endpoint demonstrating a 55% reduction in the composite rate of Level 2 and Level 3 hypoglycemic events compared to placebo (p=0.000003). In addition, LUCIDITY met all secondary endpoints demonstrating consistent, highly statistically significant, and clinically meaningful reductions in Level 2 hypoglycemic events by self-monitoring of blood glucose (SMBG), Level 2 hypoglycemic events by continuous glucose monitoring (CGM), and 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 Endocrine Society member Marilyn Tan, MD, principal investigator of the LUCIDITY clinical trial and clinical professor at the 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. Preventing even one Level 2 or Level 3 event is medically meaningful. I am excited by the LUCIDITY results announced today and the potential to have the first treatment for patients with PBH.”
“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. Preventing even one Level 2 or Level 3 event is medically meaningful. I am excited by the LUCIDITY results announced today and the potential to have the first treatment for patients with PBH.”
Marilyn Tan, MD, principal investigator, LUCIDITY clinical trial; clinical professor, Stanford School of Medicine
“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 Endocrine Society member Camille L. Bedrosian, MD, chief medical officer at Amylyx. “Together with the positive data generated across five previous clinical trials of avexitide in PBH, we believe the LUCIDITY results bring us one step closer to potentially delivering the first approved treatment for people living with PBH. We are moving with urgency to submit an NDA to the FDA by the end of the year. In the meantime, the LUCIDITY open-label extension remains ongoing, and our avexitide expanded access program, which launched in May, will continue to provide access for eligible individuals.”
The Phase 3 LUCIDITY trial enrolled 78 adult participants with PBH following RYGB surgery. Participants were randomized 3:2 to receive either 90 mg avexitide subcutaneously once daily or placebo. LUCIDITY met the primary endpoint demonstrating a 55% reduction (p=0.000003) in the composite rate of Level 2 and Level 3 hypoglycemic events compared to placebo through Week 16. LUCIDITY also met all secondary endpoints demonstrating consistent, highly statistically significant, and clinically meaningful reductions across SMBG-measured Level 2 events, CGM-measured Level 2 events, and independently adjudicated Level 3 events.
Avexitide was generally well-tolerated through the double-blind study period with a consistent and favorable safety profile replicated across all PBH clinical trials completed to date. The majority of adverse events in LUCIDITY were mild to moderate, and there were no serious adverse events related to avexitide treatment. The most common adverse events were diarrhea, injection site erythema, and injection site bruising. There were no changes in body weight observed in either the avexitide or placebo groups over the 16-week, double-blind period of the LUCIDITY trial.
“Together with the positive data generated across five previous clinical trials of avexitide in PBH, we believe the LUCIDITY results bring us one step closer to potentially delivering the first approved treatment for people living with PBH.
Camille L. Bedrosian, MD, chief medical officer, Amylyx
“We are deeply grateful to the people living with PBH who participated in LUCIDITY, their families and care partners, trial investigators, and the broader PBH community who have made the trial possible and have been so open in sharing their experiences to build understanding and awareness of the everyday impact of this condition,” said Justin Klee and Joshua Cohen, Co-CEOs of Amylyx. “Today’s data represent an exciting outcome for the PBH community and mark an important milestone as we work toward what could be the first approved treatment option for this condition. 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.”
Amylyx plans to submit a New Drug Application (NDA) to the FDA by the end of 2026. The FDA previously granted avexitide Breakthrough Therapy Designation for PBH. LUCIDITY’s 32-week open label extension (OLE) remains ongoing. The avexitide expanded access program (EAP) also remains ongoing. The Company plans to present the data from LUCIDITY at an upcoming medical meeting.
