Phase 2b results of avexitide (Eiger BioPharmaceuticals) in patients with post-bariatric hypoglycemia (PBH) and hyperinsulinemic hypoglycemia (HH) after gastric bypass, vertical sleeve, total gastrectomy or Nissen fundoplication procedures, have demonstrated statistically significant reductions in hypoglycaemia and meeting the primary and secondary endpoints of the study. The data were presented by Dr Marilyn Tan, Clinical Associate Professor of Medicine at Stanford University School of Medicine, in an oral presentation at the Endocrine Society (ENDO) 2022 meeting in Atlanta, GA.
"Patients suffering from hypoglycaemia after bariatric and other gastrointestinal surgeries often experience debilitating symptoms and worsening in quality of life. With no approved treatments, current approaches such as nutrition therapy or off-label use of pharmacotherapies have limited efficacy and are often poorly tolerated," said Tan. "Avexitide led to a significant reduction in the occurrence and extent of hypoglycaemia, confirming results previously observed in gastric bypass patients, and demonstrated comparable or greater responses among patients with severe hypoglycaemia after sleeve gastrectomy, total gastrectomy or Nissen fundoplication. GLP-1 antagonism with avexitide represents a logical therapeutic approach, based on the role of GLP-1 in mediating hyperinsulinemic hypoglycemia, and I look forward to its continued development as a treatment option that could make a meaningful difference in the lives of patients."
Avexitide is an investigational, first-in-class glucagon-like peptide-1 receptor (GLP-1r) antagonist in development for the treatment of congenital hyperinsulinism (HI) and post-bariatric hypoglycemia (PBH). Avexitide has been granted Breakthrough Therapy designation for both HI and PBH.
By binding to the GLP-1r on pancreatic beta cells and preventing GLP-1r signaling, avexitide works upstream of beta cell insulin secretion to reduce dysregulated insulin secretion and the occurrence of hypoglycemia. By addressing underlying disease mechanisms, avexitide may offer a targeted approach to treating hypoglycaemia in patients with hyperinsulinemic hypoglycaemia, including HI and PBH.
"These data further support the potential for avexitide as a targeted treatment to prevent hypoglycaemia associated with gastrointestinal surgery, with consistent improvements observed across all surgical subtypes studied," added Dr Colleen Craig, Vice President, Metabolic Diseases, Eiger. "Together with our promising results in patient congenital hyperinsulinism, these new data build a solid foundation for the role of GLP-1 in mediating hyperinsulinemic hypoglycaemia. We are pleased to be initiating our first pivotal Phase 3 clinical program for avexitide this year."
In April, Eiger announced it is initiating the Phase 3 AVANT registrational program for avexitide in congenital hyperinsulinism (HI) this year. Avexitide has been granted Orphan Drug designation by FDA for the treatment of hyperinsulinemic hypoglycaemia (which includes HI) and has also been granted Rare Pediatric Disease designation making it eligible for a priority review voucher upon regulatory approval. Avexitide is the only investigational therapy for HI that has been granted Breakthrough Therapy designation by FDA.
This Phase 2b, open-label, investigator-initiated, cross-over study assessed the safety and efficacy of avexitide in hyperinsulinemic hypoglycemia after bariatric or other gastrointestinal surgeries. Sixteen patients with a history of recurrent hypoglycaemia refractory to medical nutrition therapy (MNT) and exhibiting at least two severe hypoglycaemia events while adhering to MNT over a 14-day period were included. Metabolic and symptomatic parameters were assessed by self-monitoring of blood glucose (SMBG), electronic diary (eDiary) and blinded continuous glucose monitoring (CGM) during 14 days of MNT as compared to 14 days of MNT + avexitide administered by subcutaneous injection at a dose of 45mg twice daily or 90mg once daily for a total of 28-days of treatment.
The primary and secondary endpoints, which measured frequency of hypoglycaemia and amount of time in hypoglycaemia, were met with statistical significance. Compared with MNT alone, avexitide 45mg twice daily and 90mg once daily reduced the rate of Level 1 hypoglycaemia (SMBG <70mg/dL) by 54% (p=0.003) and 68% (p=0.0005), respectively; Level 2 hypoglycemia (SMBG <54mg/dL) by 57% (p=0.003) and 53% (p=0.004), respectively; and Level 3 hypoglycaemia (severe event characterized by altered mental and/or physical function requiring assistance, as captured by eDiary) by 68% (p=0.0003) and 66% (p=0.0003), respectively.
Objective assessment by blinded CGM, substantiated SMBG, and eDiary results, with both dosing regimens (45mg BID and 90mg QD) demonstrating significant reductions in hypoglycaemia events (up to 65%) and time spent in hypoglycaemia (up to 64%). A greater magnitude of effect was consistently observed with once daily (90mg QD) than twice daily (45mg BID) dosing, as measured by blinded CGM.
Avexitide was well-tolerated, with no serious adverse events or participant withdrawals. The most common adverse events were diarrhoea, headache and injection site reaction/bruising.