Amylyx Pharmaceuticals Reports Positive Avexitide Trial Results Amylyx Pharmaceuticals has announced positive topline results from its Phase 3 LUCIDITY trial of Avexitide. The trial evaluated Avexitide in people with post-bariatric hypoglycemia (PBH).
The 78-participant study met its FDA-agreed-upon primary endpoint. Avexitide delivered a 55% reduction in combined Level 2 and Level 3 hypoglycemic events. The result compared Avexitide with placebo through Week 16. The trial reported a highly significant p-value of 0.000003.
In addition, LUCIDITY achieved all of its secondary endpoints. The results showed consistent reductions in several measures of hypoglycemic events. They included Level 2 events assessed by self-monitoring of blood glucose (SMBG) .
The trial also assessed Level 2 events through continuous glucose monitoring (CGM). In addition, researchers evaluated independently adjudicated Level 3 hypoglycemic events. Avexitide was generally well-tolerated during the double-blind treatment period. The treatment also showed a favorable safety profile across the study.
Amylyx Pharmaceuticals now plans to submit a New Drug Application (NDA) to the FDA. The company expects to make the submission by the end of 2026. The FDA has already granted Avexitide Breakthrough Therapy Designation for PBH. The agency has also granted Avexitide Orphan Drug Designation.
“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 Marilyn Tan, MD, FACE, 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.”
LUCIDITY Trial Demonstrates Strong Clinical Outcomes
The Phase 3 LUCIDITY trial enrolled 78 adults with PBH. All participants had previously undergone Roux-en-Y gastric bypass (RYGB) surgery. Researchers randomized participants in a 3:2 ratio. One group received 90 mg of Avexitide subcutaneously once daily. The other group received placebo.
The primary endpoint focused on the combined rate of Level 2 and Level 3 hypoglycemic events. The assessment covered the first 16 weeks of treatment. Avexitide achieved a 55% reduction in the composite rate. The study recorded a p-value of 0.000003 against placebo.
Furthermore, the treatment achieved every secondary endpoint. The results remained consistent across the different glucose monitoring methods. Researchers observed significant reductions in SMBG-measured Level 2 events. They also reported reductions in CGM-measured Level 2 events.
In addition, independently adjudicated Level 3 events declined during treatment. These findings support the potential clinical value of Avexitide for people living with PBH.
“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 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.”
Avexitide Shows Favorable Safety Profile
The company reported that Avexitide remained generally well-tolerated. Its safety profile remained consistent throughout the double-blind study period. Amylyx also reported similar safety findings across its completed PBH clinical trials. Most adverse events reported during LUCIDITY were mild or moderate.
Importantly, no serious adverse events related to Avexitide treatment occurred. The most common adverse events included diarrhea and injection site erythema. Injection site bruising also appeared among the most frequently reported adverse events. Additionally, researchers observed no body weight changes in either treatment group.
The weight assessment covered the complete 16-week double-blind period. Both the Avexitide and placebo groups showed no changes in body weight. These safety findings add further information to the clinical development program. Meanwhile, Amylyx continues to assess longer-term data through its open-label extension.
“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 Prepares FDA Submission for Avexitide
Amylyx plans to submit its NDA for Avexitide to the FDA by the end of 2026. The company has already started preparations for the regulatory submission. The FDA previously granted Avexitide Breakthrough Therapy Designation for PBH. The designation supports development programs addressing serious conditions with significant unmet medical needs.
The LUCIDITY study also includes a 32-week open-label extension. That extension remains ongoing as participants continue follow-up treatment. Amylyx launched its Avexitide expanded access program (EAP) in May. The program will continue providing access to eligible individuals.
The company also plans to present the LUCIDITY findings at an upcoming medical meeting. Further data may provide additional insight into the treatment’s clinical profile. If approved, Amylyx expects to prepare for a potential commercial launch of Avexitide in 2027. The company continues to advance its launch preparations while regulatory activities move forward.
Post-Bariatric Hypoglycemia Remains an Unmet Medical Need
Post-bariatric hypoglycemia is a chronic metabolic condition. It can develop after bariatric surgery and cause repeated drops in blood glucose. PBH is estimated to affect around 8% of people in the U.S. who undergo major bariatric procedures. These procedures include sleeve gastrectomy and Roux-en-Y gastric bypass.
The population affected is approximately 160,000 people in the United States. PBH is thought to be related to an exaggerated GLP-1 response to food ingestion. That response can cause too much insulin secretion. Consequently, patients may have episodes of rapid and repeated falls in blood glucose.
These hypoglycemic episodes can become persistent and disabling. They can also influence patient safety and day-to-day quality of life. The American Diabetes Association (ADA) states that hypoglycemia may be a medical emergency. Low blood sugar may interfere with important functions of the body.
Neuroglycopenia may also occur with PBH-related hypoglycemia. This occurs when the brain is receiving inadequate glucose. Patients may be confused and have impaired cognition. Severe attacks can also cause loss of consciousness or seizures.
A condition can thus cause a serious disability. It may influence independent living, nutritional status and overall safety. PBH has a large disease burden, but there are no FDA-approved treatments for it. This treatment gap suggests the potential importance of novel approaches to therapy.
About the Phase 3 LUCIDITY Trial
LUCIDITY is a 78-participant Phase 3 clinical trial. The study is identified by ClinicalTrials.gov number NCT06747468. The multicenter study used a randomized, double-blind, placebo-controlled design. It evaluated the efficacy and safety of Avexitide in adults with PBH.
All of the participants had undergone RYGB surgery. The trial was conducted at 21 clinical sites across the United States. Participants received Avexitide 90 mg once daily or placebo. The treatment was administered subcutaneously by researchers.
The study included a screening period of up to six weeks. This period included a 3-week run-in period. Double-blind treatment period was 16 weeks. Participants were then eligible to continue into a 32-week open-label extension.
The primary efficacy objective focused on the FDA-agreed-upon outcome. Researchers evaluated the reduction in combined Level 2 and Level 3 hypoglycemic events. The assessment covered the period through Week 16. The study also evaluated treatment safety and tolerability.
The positive topline findings strengthen the clinical development case for Avexitide. Amylyx now moves toward its planned NDA submission to the FDA. The company will continue monitoring participants through the open-label extension. Meanwhile, its expanded access program will remain available to eligible individuals. The latest LUCIDITY results mark a significant development in Amylyx’s PBH program. They also highlight continued efforts to address an important unmet medical need.
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News Source: Businesswire.com
