Eiger BioPharmaceuticals has announced positive results from the Phase 2 PREVENT study of Avexitide in patients with severe Post-Bariatric Hypoglycaemia (PBH), the outcomes were published in Journal of Clinical Endocrinology & Metabolism (Craig, C.M. et al, 2021).
PREVENT is the first randomized placebo-controlled study to evaluate the efficacy of a pharmacologic agent for patients with PBH in the outpatient setting. PREVENT investigated the safety and efficacy of Avexitide administered as 30mg twice daily (BID) or 60mg once daily (QD) subcutaneous (SC) injections in post-bariatric surgical patients who experience chronic, dangerously low, postprandial blood glucose levels, known as post-bariatric hypoglycaemia or PBH.
Eighteen patients with refractory, severe PBH were enrolled across five US academic centers and dosed as outpatients in the PREVENT study. Patients with severe PBH experience frequent postprandial episodes of hypoglycaemia accompanied by neuroglycopenic signs and symptoms, including altered mental status, visual changes, motor incoordination, loss of consciousness, and seizures, putting patients at risk for injury or death from falls, motor vehicle accidents, or prolonged hypoglycaemia and rendering many unable to drive, work, live alone, or care for dependents. Avexitide is a targeted, first-in-class, GLP-1 antagonist in development for the treatment of hyperinsulinemic hypoglycaemia conditions, including PBH and congenital hyperinsulinism (CHI), disorders for which there are no approved treatments.
Primary endpoint was met with statistical significance by both dosing regimens. During hypoglycaemia provocation in the clinical setting, the mean plasma glucose nadir was increased by 21% (p=0.001) and 26% (p=0.0002) following Avexitide 30 mg and 60 mg dosing, respectively, compared to placebo, corresponding to 50% and 75% fewer participants requiring rescue. Consistent with Avexitide's mechanism of action, peak insulin was reduced by 23% (p=0.029) and 21% (p=0.042) following Avexitide 30mg and 60mg dosing, respectively.
Metabolic and clinical parameters were also monitored during each patient's daily routine in the outpatient setting as assessed by self-blood glucose monitoring (SBGM), electronic diary, and blinded continuous glucose monitoring (CGM). Patients experienced significantly fewer Levels 1-3 hypoglycaemia events during Avexitide treatment, defined, respectively as SBGM <70 mg/dL, SMBG <54 mg/dL, and a severe event characterized by altered mental and/or physical functioning requiring assistance. Patients also demonstrated reductions in percent time in hypoglycaemia during diurnal periods (8 am to midnight) and number of hypoglycaemia events as measured by CGM.
Avexitide was well-tolerated in this study. The most common adverse events were injection site bruising, nausea, and headache, all of which occurred with lower frequency during Avexitide vs. placebo treatment.
"Avexitide treatment demonstrated significant and consistent improvements across multiple clinical and metabolic parameters, as measured both in the clinical setting during hypoglycemia provocation and in the patient home setting under 'real world' conditions. Significant improvements in primary and secondary endpoints were observed, with reductions in postprandial hyperinsulinemic hypoglycemia during mixed meal provocation," said Dr Colleen Craig, Avexitide Program Lead at Eiger. "Significant improvements were also observed in the home setting, with fewer hypoglycemia events and less time spent with dangerously low glucose levels. Avexitide may represent a first promising treatment for patients with severe PBH."
Eiger has received concurrence from FDA and EMA on a single Phase 3, registration-enabling study of Avexitide in PBH, including overall study design, study size and endpoints.
Avexitide is a well-characterized, first-in-class, 31-amino acid GLP-1 antagonist that selectively targets and blocks GLP-1 receptors, normalizing insulin secretion by the pancreas, and thereby reducing postprandial hypoglycaemia. Avexitide is Phase 3 ready and has received concurrence from FDA and EMA on a single Phase 3, registration-enabling study of Avexitide in severe PBH Avexitide has been granted Breakthrough Therapy Designation by the FDA, as well as Orphan Drug Designation in the US by the FDA for the treatment of hyperinsulinemic hypoglycaemia and Orphan Drug Designation by the EMA for the treatment of non-insulinoma pancreatogenous hypoglycaemia syndrome (NIPHS). Both of these orphan designations include PBH. Avexitide has never been approved or commercialised for any indication.