During normal digestion, dietary carbohydrates convert into glucose that circulates in the blood. Insulin functions like a key, unlocking muscle and fat cells so they can absorb glucose for energy while storing excess in the liver. When blood sugar drops, healthy pancreatic cells suppress insulin secretion, signaling the liver to release stored glucose back into the bloodstream to maintain equilibrium.
In patients with congenital hyperinsulinism (CHI), this homeostatic feedback loop fails. The pancreas continues secreting insulin even when blood sugar levels fall precipitously. As cells continuously consume remaining glucose while hepatic glucose release is blocked, patients suffer severe, recurrent hypoglycemia. Furthermore, excessive insulin suppresses the production of ketone bodies—an emergency alternative fuel source for the brain.
Without prompt intervention, prolonged or repeated severe hypoglycemia in infants and young children can trigger seizures, loss of consciousness, and permanent neurological damage. Treatment options remain severely limited. In the United States, diazoxide is the sole drug approved for hyperinsulinemic hypoglycemia. However, therapeutic response varies widely depending on underlying genetic mutations, and the drug is associated with significant adverse effects, including hirsutism (excessive hair growth), fluid retention, and potentially fatal pulmonary hypertension in infants. When medical therapy fails, patients often face off-label drug regimens or partial pancreatectomy (surgical removal of the pancreas).
To address this high unmet need, Hanmi Pharmaceutical is developing efpeglucagon (HM15136), a novel investigational therapy designed to prevent hypoglycemia through a mechanism distinct from traditional insulin suppressors.
A Long-Acting Glucagon Approach to Counteract Excess Insulin
Efpeglucagon utilizes long-acting technology to extend the bioactivity of glucagon, a natural counter-regulatory hormone that opposes insulin by stimulating the liver to release stored glucose into the bloodstream.
While emergency glucagon has long been used to rescue acute severe hypoglycemia, conventional aqueous formulations are chemically unstable, forming precipitates or clogging infusion lines during prolonged administration. Hanmi engineered efpeglucagon as a stabilized, once-weekly subcutaneous injection, aiming to introduce the world's first weekly glucagon-class therapy for congenital hyperinsulinism.
Hanmi announced Sept. 4 that it has completed the primary dosing period for its global Phase 2 clinical trial evaluating efpeglucagon in patients aged 2 and older with CHI. Full data analysis is currently underway.
Interim Data Shows 72% Reduction in Hypoglycemic Episodes
The Phase 2 study evaluates safety, pharmacokinetics, and efficacy in reducing hypoglycemic events when efpeglucagon is added to existing regimens in patients with refractory disease.
Interim results from an initial cohort of eight patients—disclosed last year at a joint scientific meeting of the European Society for Paediatric Endocrinology (ESPE) and the European Society of Endocrinology (ESE)—demonstrated a sharp reduction in hypoglycemia. Based on seven daily fingertip blood glucose checks, average weekly hypoglycemic episodes fell by 72.3%, dropping from 10.1 episodes at baseline to 2.8 after eight weeks of treatment. Additional home-monitoring data revealed a 77.5% decline, from 16.0 to 3.6 weekly episodes.
The most common adverse events were mild-to-moderate gastrointestinal symptoms—including abdominal pain, diarrhea, nausea, and vomiting—alongside transient hyperglycemia and decreased appetite. No treatment-related deaths or discontinuations occurred within the initial cohort.
Reflecting its clinical potential, efpeglucagon received Breakthrough Therapy designation from the U.S. Food and Drug Administration (FDA) in February, a program offering expedited development and regulatory review. The drug candidate has also earned Orphan Drug designations for CHI from the U.S. FDA, the European Medicines Agency (EMA), and South Korea's Ministry of Food and Drug Safety (MFDS), alongside Rare Pediatric Disease designation by the FDA and EMA Orphan Drug status for insulin autoimmune syndrome.
Hanmi will present baseline demographic and clinical characteristics of enrolled Phase 2 patients during an oral presentation on Sept. 9 at the 64th Annual Meeting of the European Society for Paediatric Endocrinology (ESPE 2026) in Marseille, France (Sept. 8–10).
"We have completed the primary dosing period for efpeglucagon's global Phase 2 clinical trial," said Lee Moon-hee, Executive Director and Head of Clinical Operations at Hanmi Pharmaceutical. "At ESPE 2026, we will detail the demographic and baseline clinical profiles of the Phase 2 patient cohort as we analyze the comprehensive dataset to advance patient-centered care for this rare disorder."
