Amylyx Pharmaceuticals has completed the acquisition of avexitide, a first-in-class glucagon-like peptide-1 (GLP-1) receptor antagonist, from Eiger BioPharmaceuticals for $35.1 million. The investigational therapy has received FDA Breakthrough Therapy Designation for treating hyperinsulinemic hypoglycemia conditions, positioning it for a Phase 3 clinical trial launch in the first quarter of 2025.
Addressing Critical Unmet Medical Need
Avexitide targets hyperinsulinemic hypoglycemia, a condition where excessive insulin production leads to dangerously low blood sugar levels. The drug has shown particular promise in treating post-bariatric hypoglycemia (PBH), which affects approximately 8% of patients who have undergone bariatric surgery, and congenital hyperinsulinism (HI), a rare pediatric condition.
"PBH is a debilitating condition with no approved treatment options," said Dr. Camille L. Bedrosian, Chief Medical Officer of Amylyx. The condition affects an estimated 160,000 Americans and can cause severe complications including impaired cognition, cardiac arrhythmias, loss of consciousness, and seizures due to brain glucose starvation.
Strong Clinical Trial Results
Avexitide has demonstrated significant efficacy across five Phase 2 clinical trials. In the randomized, placebo-controlled crossover PREVENT study, avexitide showed statistically significant reductions in hypoglycemic events. The 30 mg twice daily dose resulted in 50% fewer participants requiring rescue during mixed meal tolerance testing, while the 60 mg once daily dose achieved a 75% reduction.
A subsequent Phase 2b open-label study in 16 participants with PBH following various surgical procedures showed even more impressive results. Avexitide reduced the frequency of hypoglycemia by up to 65% and decreased time spent in hypoglycemia by up to 64%. The study met both its primary endpoint of reducing diurnal Level 2 hypoglycemia events and all secondary endpoints.
Mechanism of Action and Safety Profile
Avexitide works by binding to GLP-1 receptors on pancreatic islet beta cells, blocking excessive GLP-1 effects that lead to insulin hypersecretion. In PBH patients, this mechanism helps stabilize glucose levels and prevent the rapid blood sugar drops characteristic of the condition.
The drug demonstrated a favorable safety profile across clinical trials. Common adverse events included injection site bruising, headache, nausea, and diarrhea, which were generally mild to moderate and resolved without medical treatment. Notably, no participants withdrew from studies due to adverse events, and no serious adverse events were reported in the Phase 2b trial.
Regulatory Recognition and Development Timeline
The FDA has granted avexitide multiple designations recognizing its therapeutic potential: Breakthrough Therapy Designation for both PBH and congenital HI, Rare Pediatric Disease Designation for congenital HI, and Orphan Drug Designation for hyperinsulinemic hypoglycemia treatment. FDA guidance suggests that reduction in hypoglycemia events could serve as an endpoint to support approval following positive Phase 3 results.
Amylyx Co-CEOs Joshua Cohen and Justin Klee emphasized the strategic alignment of the acquisition: "When we reviewed all the compelling data supporting avexitide, it clearly aligned with our strategic scientific criteria, expertise, and community values."
Expanding Treatment Portfolio
The avexitide acquisition strengthens Amylyx's focus on endocrine and neuroscience treatments, complementing its existing pipeline that includes AMX0035 for Wolfram syndrome and progressive supranuclear palsy, and AMX0114, an antisense oligonucleotide targeting calpain-2 for ALS treatment.
For congenital HI, Amylyx is actively engaging with the medical community to develop a clinical pathway based on promising Phase 2 results from studies conducted at Children's Hospital of Philadelphia. The company has assumed certain contractual obligations from the acquisition, including a 3% royalty on future avexitide sales in PBH to academic institutions.
The acquisition positions Amylyx to address a significant gap in treatment options for patients suffering from hyperinsulinemic hypoglycemia, a condition that can severely impact quality of life and lead to dangerous complications including falls, motor vehicle accidents, and job loss due to unpredictable hypoglycemic episodes.
