Amylyx Pharmaceuticals Eyes Q3 Phase 3 Avexitide Readout as PBH Launch Plans Take Shape

Key Points

• Amylyx expects Phase 3 topline results for avexitide in Q3 as it advances the drug for post-bariatric hypoglycemia, a condition with no approved treatments and an estimated 160,000 U.S. patients.
• The company says the higher 90 mg dose showed better around-the-clock coverage in earlier testing, and the Phase 3 study is designed to measure reductions in severe hypoglycemic events using FDA-recognized endpoints.
• Commercial planning is already underway, with Amylyx targeting a potential 2027 launch, building out its NDA and pre-commercial strategy, while saying it has cash runway into 2028.

Amylyx Pharmaceuticals NASDAQ: AMLX Co-Chief Executive Officer Justin Klee said the company is preparing for a key Phase 3 readout for avexitide, its lead program for post-bariatric hypoglycemia, during an appearance at the Goldman Sachs Global Healthcare Conference.

Klee described avexitide as a first-in-class GLP-1 receptor antagonist being developed for post-bariatric hypoglycemia, or PBH, a condition he said affects about 160,000 people in the U.S. He said the company expects that population to grow over time.

PBH is characterized by persistent, symptomatic severe hypoglycemia, Klee said, including neuroglycopenia, in which the brain does not receive enough glucose. He said patients can experience severe confusion, loss of consciousness and seizures, and that there are currently no approved treatments for the condition.

Klee said PBH is driven by elevated GLP-1 response after bariatric surgery, with some patients producing 10 to 20 times normal GLP-1 levels. That can cause insulin spikes and severe hypoglycemia. Avexitide is designed to block the GLP-1 receptor and reduce downstream hypoglycemia.

Phase 3 Readout Expected in Third Quarter

Klee said Amylyx expects topline results from its Phase 3 pivotal trial of avexitide in the third quarter. The company completed enrollment at the end of March, and the study includes a 16-week double-blind, placebo-controlled period, followed by time for database cleaning, lock and analysis.

The Phase 3 trial is testing a 90 mg dose of avexitide. Klee said an earlier 60 mg dose showed effectiveness, but investigators observed possible breakthrough hypoglycemic events late at night or early in the morning. Pharmacokinetic analysis suggested coverage could be improved, leading to the higher dose.

He said the 90 mg dose provided coverage across the full day and night cycle in a Phase 2b trial, where the company observed reductions in both daytime and nighttime hypoglycemia as measured by continuous glucose monitoring, along with what he described as a good safety profile.

Klee said the Phase 3 trial was designed to be consistent with earlier studies, including the requirement that participants have frequent hypoglycemic events during a run-in period. He said the study is 90% powered to detect a 35% relative difference in Level 2 and Level 3 hypoglycemic events, compared with a 64% treatment effect observed in Phase 2b.

Trial Conduct and Endpoint Measurement

Klee addressed investor questions about trial conduct, saying the primary endpoint is a composite of Level 2 and Level 3 hypoglycemic events. Level 2 events are measured by finger-stick blood glucose readings below 54 mg per deciliter, while Level 3 events involve the need for independent rescue.

Participants complete diary entries, and Level 3 events are reviewed by an adjudication committee of expert endocrinologists using a charter that Klee said was reviewed by the U.S. Food and Drug Administration. He also noted that FDA guidance recognizes the endpoint and that avexitide has received Breakthrough Therapy designation.

Klee said Amylyx can monitor trial data nearly in real time, including finger-stick readings, diaries and blinded continuous glucose monitor data. The company uses that information to assess whether participants are consistently capturing events and following study procedures.

He also discussed dietary behavior, saying participants are trained and retrained on diet, and must certify at every visit that they are following guidance. Klee said some diet liberalization occurred in earlier Phase 2 work, but that avexitide still produced a 55% reduction in hypoglycemic events in the first Phase 2 trial.

Commercial Planning Underway

Klee said Amylyx is preparing for a potential launch in 2027 if the Phase 3 study is successful. He said the company is already working on its new drug application and pre-commercial activities.

He characterized PBH as a rare disease with significant unmet need and said Amylyx is seeing growing awareness among endocrinologists. Klee said PBH is now included on endocrinology board exams and that an ICD-10 code for PBH is expected to be adopted in October.

Current care is centered on medical nutrition therapy, Klee said, including frequent small meals and avoidance of simple carbohydrates. He said physicians use a variety of off-label medications, but said they do not address the GLP-1 mechanism that Amylyx believes is central to PBH.

Klee said Amylyx is refining its go-to-market strategy and expects to focus early efforts on centers that treat large numbers of PBH patients, including academic and large endocrinology centers. He said the company is thinking about its commercial infrastructure in a rare disease framework, including field teams and digital tools.

On pricing, Klee said there are no direct analogs for PBH, but cited recent rare endocrine drug launches as potential reference points. He said Amylyx expects to work with payers to support access.

Long-Acting GLP-1 Antagonist and ALS Pipeline

Klee said Amylyx is also developing AMX0318, a potential once-weekly, long-acting GLP-1 receptor antagonist. The program is in IND-enabling studies, and the company’s goal is to move it into the clinic next year. Amylyx is developing the molecule through a collaboration with Gubra, which Klee described as an expert in peptide drug development.

He said avexitide’s composition claims extend to 2037 before potential patent term extension, which could add another two to three years. Klee said further innovation, including AMX0318, could support additional intellectual property.

Klee also discussed AMX0114, Amylyx’s calpain-2 program for ALS. The intrathecally administered antisense oligonucleotide is in a multiple ascending dose study in people with ALS. Klee said the company has completed the first two dosing cohorts, is moving to cohort 3 and plans to present biomarker results from the lowest-dose cohort at an ALS conference this month.

Cash Runway Into 2028

Klee said Amylyx has cash runway into 2028. He said that guidance includes work leading up to and through a potential 2027 commercialization of avexitide, including field team buildout, inventory and launch preparations intended to support access for PBH patients.

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.

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