Amylyx's Avexitide Phase III Win Sets Up FDA Filing for PBH Treatment

Key Points

• Avexitide met all Phase III endpoints in post-bariatric hypoglycemia (PBH), reducing serious Level 2 and Level 3 hypoglycemic events by 55% with a highly significant p-value. The treatment was generally safe and well tolerated.
• Amylyx plans to submit a New Drug Application to the FDA before year-end and is preparing for a potential commercial launch, with management discussing a possible 2027 timeframe.
• The company estimates about 160,000 U.S. patients have PBH, though the eventual FDA label could initially be limited to roughly 120,000 patients whose condition followed Roux-en-Y gastric bypass surgery.

Amylyx Pharmaceuticals NASDAQ: AMLX said its Phase III trial of avexitide in post-bariatric hypoglycemia, or PBH, met its primary endpoint and all secondary endpoints, positioning the company to submit a New Drug Application to the U.S. Food and Drug Administration before year-end.

PBH is a chronic condition that can develop years after bariatric surgery and is marked by recurrent episodes of low blood sugar. According to Co-CEO and Co-Founder Josh Cohen, episodes may occur after meals, during exercise or stress, or without an identifiable trigger. Severe episodes can lead to loss of consciousness, seizures, dizziness and confusion.

Cohen said Amylyx estimates that roughly 8% of people who undergo bariatric surgery develop PBH, representing approximately 160,000 people in the United States. The company said about 90% of affected people describe themselves as disabled by the condition.

Phase III Results and Regulatory Plans

The company said avexitide reduced Level 2 and Level 3 hypoglycemic events by 55% in its Phase III trial, meeting the pre-specified primary endpoint with a reported p-value of 0.000003. The American Diabetes Association characterizes such events as medical emergencies, according to Cohen.

Justin Klee, Amylyx's Co-CEO and Co-Founder, said the treatment also met secondary endpoints measuring Level 2 events, Level 3 events and continuous glucose-monitoring, or CGM, outcomes. He said the consistency across measures was a key point in discussions with the company's clinical steering committee.

"Each component is telling you something slightly different, but each way you look at it's a very strong signal," Klee said, adding that the drug was generally safe and well tolerated in a manner consistent with prior trials.

Cohen said all eligible patients enrolled in the trial's open-label extension, which he described as encouraging from both an efficacy and safety standpoint. Amylyx is working to present and potentially publish the complete dataset, with the goal of doing so before the end of the year.

The company said it had begun work on its NDA before receiving the Phase III results. Cohen said Amylyx expects to submit the application before year-end and is preparing for a potential commercial launch. During the discussion, management referred to launch preparations for 2027 and, later, to a potential launch next year.

Potential Label and Addressable Population

Amylyx's Phase III trial enrolled patients whose PBH followed Roux-en-Y gastric bypass surgery. However, Klee said the company believes the condition's underlying pathophysiology is similar regardless of the bariatric procedure that preceded it, including sleeve gastrectomy.

The eventual FDA indication remains uncertain, he said. A label could potentially specify PBH following Roux-en-Y gastric bypass or more broadly encompass PBH associated with bariatric surgery. Klee noted that avexitide was evaluated in a Phase IIb study involving people who had undergone a variety of surgeries, and the company observed similar results across surgery types.

If the eventual label is limited to Roux-en-Y gastric bypass patients, Amylyx estimates that about 120,000 of the approximately 160,000 U.S. PBH patients fall into that group. Klee said the company believes it could conduct an efficient additional trial if needed to support use across other surgery types.

Management said its 160,000-patient estimate was derived from multiple sources, including long-term prospective studies, claims analyses and clinic surveys. Cohen said the claims analysis examined patients who had bariatric surgery and later experienced hypoglycemia claims not explained by another medical condition.

Commercial Considerations

Amylyx characterized PBH as a “large rare disease” and said endocrinologists appear to have substantial awareness of the condition. Klee said PBH is included on endocrinology board examinations and that physicians at the ENDO conference reported seeing significant numbers of patients with limited treatment options beyond dietary counseling.

Management cautioned against viewing emergency-room visits as the only marker of patients who may need treatment. Cohen said hypoglycemia-related emergency visits can be difficult to identify in claims data because they may be coded under outcomes such as loss of consciousness, falls, broken bones or car accidents. He said endocrinologists generally aim to reduce recurrent hypoglycemic events regardless of whether a patient recently visited an emergency room.

The company has not yet provided pricing plans for avexitide. Cohen said Amylyx is studying comparable rare endocrine and broader rare-disease product launches, while noting that no single product represents a perfect commercial analog.

Looking ahead, management said it expects the PBH population to grow as bariatric procedures continue to be performed and because PBH does not appear to resolve once it develops. The company is also advancing AMX0318, a long-acting GLP-1 receptor antagonist for PBH, through IND-enabling studies, with an investigational new drug filing targeted for next year.

About Amylyx Pharmaceuticals (NASDAQ:AMLX)

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