Amylyx Buys FDA-Designated Phase 3 GLP-1 Antagonist Avexitide

Amylyx Pharmaceuticals, Inc. has announced the acquisition of avexitide, a novel, first-in-class GLP-1 receptor antagonist from Eiger BioPharmaceuticals, Inc. Avexitide is under investigation for its potential to treat hyperinsulinemic hypoglycemia, which includes post-bariatric hypoglycemia (PBH) and congenital hyperinsulinism (HI). The U.S. Food and Drug Administration (FDA) has granted avexitide Breakthrough Therapy Designation for both PBH and congenital HI, recognizing its potential to address significant unmet medical needs.

Avexitide works by binding to the GLP-1 receptor on pancreatic islet beta cells, thereby blocking the GLP-1 hormone's effect. This action helps decrease insulin secretion and stabilizes blood glucose levels, which can mitigate hypoglycemia. In conditions like PBH, an excess of GLP-1 can result in hypersecretion of insulin, leading to severe hypoglycemic episodes. These episodes can manifest in various symptoms, including dizziness and loss of consciousness, if left untreated.

Clinical trials have shown promising results for avexitide. In Phase 2 studies of patients with PBH, avexitide demonstrated statistically significant reductions in hypoglycemic events. These trials included two different dosage regimens, 30 mg twice daily (BID) and 60 mg once daily (QD). The trials showed that avexitide significantly increased mean plasma glucose levels and reduced insulin peaks, thus lowering the incidence of severe hypoglycemic events. Additionally, continuous glucose monitoring (CGM) showed reductions in time spent in hypoglycemia without causing clinically relevant hyperglycemia.

Moreover, avexitide was generally well tolerated across five clinical trials, with the most common adverse events being injection site bruising, headache, and nausea. These adverse effects occurred more frequently with placebo than with avexitide, and no participants withdrew due to adverse events.

Amylyx is set to begin a Phase 3 program for avexitide in PBH in the first quarter of 2025, with data expected by 2026. The FDA has agreed to the primary endpoint for this Phase 3 trial, indicating regulatory support for the continued development of avexitide. Amylyx is also engaging with the congenital HI community and experts to chart a path forward for developing avexitide based on promising Phase 2 study results from the Children’s Hospital of Philadelphia.

In addition to avexitide, Amylyx has other pipeline programs under development. These include AMX0035, an oral fixed-dose combination for treating neurodegenerative diseases like Wolfram syndrome and progressive supranuclear palsy, and AMX0114, an antisense oligonucleotide targeting calpain-2 for treating amyotrophic lateral sclerosis (ALS).

The acquisition of avexitide aligns with Amylyx’s strategic focus on addressing high unmet medical needs in both endocrine and neuroscience fields. Amylyx has always emphasized a rigorous scientific approach and community-centered values, and the addition of avexitide to its pipeline reinforces its commitment to delivering important treatment options to communities in need.

In summary, the acquisition of avexitide from Eiger BioPharmaceuticals signifies a significant step forward for Amylyx Pharmaceuticals. With the clinical trials showing positive results and the backing of the FDA, avexitide holds promise as a treatment for conditions characterized by hyperinsulinemic hypoglycemia, such as PBH and congenital HI. The continued development and upcoming Phase 3 trials will determine its efficacy and safety further, potentially providing a much-needed therapeutic option for affected patients.