Amylyx Pharmaceuticals Acquires Phase III-Ready GLP-1 Receptor Agonist Avexitide for Hyperinsulinemic Hypoglycemia from Eiger BioPharmaceuticals

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Amylyx Pharmaceuticals has acquired Eiger BioPharmaceuticals’ avexitide, a Phase III-ready GLP-1 receptor antagonist being developed for the treatment of hyperinsulinemic hypoglycemia. According to the company, the treatment has received Breakthrough Therapy Designation by the FDA for a number of indications including post-bariatric hypoglycemia (PBH) and congenital hyperinsulinism (HI). The drug works by targeting the GLP-1 receptor on pancreatic islet beta cells, aiming to decrease insulin secretion and stabilize glucose levels.¹

“Since Amylyx was founded, we have been guided by a rigorous approach to our science to bring potential treatments to communities with high unmet needs. When we reviewed all the compelling data supporting avexitide, it clearly aligned with our strategic scientific criteria, expertise, and community values, and we are excited to build upon the important work done to date to study this asset,” said Joshua Cohen and Justin Klee, co-CEOs, Amylyx, in a press release.

The Phase II, randomized, placebo-controlled, crossover PREVENT trial aimed to evaluate the efficacy and safety of avexitide for the treatment of PBH following Roux-en-Y gastric bypass surgery. The primary endpoint of the study was an increase in mean plasma glucose nadir. Results from this trial demonstrated that avexitide 30 mg twice daily and 60 mg twice daily increased mean plasma glucose nadir by 21% versus placebo for the 30 mg cohort and 26% for the 60 mg cohort.

Further, it lowered insulin peak significantly compared to placebo, specifically 23% in the 30 mg group and 21% in the 60 mg group, which equaled 50% and 75% fewer participants requiring rescue during mixed meal tolerance testing, respectively. Notable reductions in rates of levels one, two, and three hypoglycemia were also observed.

An additional Phase IIb open-label, investigator-initiated, crossover study of higher dose avexitide (45 mg BID and 90 mg QD) enrolled 16 patients with PBH following Roux-en-Y gastric bypass surgery, vertical sleeve gastrectomy, esophagectomy, Nissen fundoplication, or gastrectomy. The trial hit its primary endpoint, which was the number of diurnal level two hypoglycemia events (glucose <54mg/dL) as measured by continuous glucose monitoring. Results in the 45 mg BID group found a 54% decrease from baseline in the rate of level one hypoglycemia, 57% for the rate of level two hypoglycemia, and 68% for the rate of level three severe hypoglycemia. In the 90 mg QD group, the decrease at level one was 68%, 53% at level two, and 66% for level three.

Adverse events (AEs) were reported to be mostly mild to moderate and resolved without medical treatment, with no serious AEs occurring. Common AEs included diarrhea, headache, bloating, and injection site reaction/bruising.¹

“PBH is a debilitating condition with no approved treatment options, and we look forward to advancing this critical work with avexitide into Phase III for individuals with PBH based on the totality of data from five clinical trials, and informed by our ongoing work to address endocrine and metabolic aspects of Wolfram syndrome. We also are continuing our conversations with the congenital HI community regarding the clinical development of avexitide in congenital HI to develop a path forward,” said Camille L. Bedrosian, MD, chief medical officer, Amylyx, in the press release. “While we are excited to study this new scientific pathway in hyperinsulinemic hypoglycemia, our research in ALS and other neurodegenerative diseases continues through our AMX0035 and AMX0114 programs, guided by the understanding that people living with these devastating diseases have no time to wait – we must continue to research and collaborate with urgency.”

Amylyx plans to start Phase III trials for PBH in early 2025 and is collaborating with experts to advance treatment for congenital HI.¹

Reference

1. Amylyx Pharmaceuticals Announces Acquisition of Phase 3-ready GLP-1 Receptor Antagonist (Avexitide) with FDA Breakthrough Therapy Designation. Business Wire. July 10, 2024. Accessed July 12, 2024. https://www.businesswire.com/news/home/20240710172870/en