ESPE Abstracts

Background: Congenital hyperinsulinism (CHI) is a rare disease affecting neonates, infants, and children. CHI is characterized by dysregulated insulin secretion resulting in severe recurrent hypoglycemia. Early treatment is necessary to limit the risk of neurologic and developmental sequelae. Current treatment options are limited and inadequate. Dasiglucagon (DASI) is a glucagon analog suitable for continuous subcutaneous infusion which has been shown to raise blood glucose in a dose dependent manner.

Study Design and Objectives: This phase 2/3 trial evaluated the efficacy and safety of DASI in children with CHI ages ≥7 days and <12 months of age with intravenous glucose requirements ≥ 10 mg/kg/min. The study was a 2-period crossover (treatment periods 48 hours each), double-blind, placebo-controlled trial (Part 1) followed by open-label, single-arm DASI treatment (Part 2). Participants were treated with DASI or placebo (by continuous subcutaneous infusion) in random order. Study drug and glucose infusion rate (GIR) were adjusted per protocol to maintain plasma glucose in the normal range. Primary endpoint in Part 1 was GIR during the last 12 hours of treatment during each 48-hour treatment period. Additional endpoints included total carbohydrate (IV and gastric).

Study Results: A total of 12 children (age 0.5-10.7 months, mean 2.4) were enrolled. Mean GIR for the 12 hours prior to initiation of treatment was 15.7 ± 4.5 mg/kg/min (mean ± SD). The results for the primary endpoint in Part 1 are shown in the table below.

DASI significantly reduced GIR in the last 12 hours of treatment with a relative reduction in IV GIR of -55% as compared to placebo. DASI also reduced GIR over the entire 48-hour treatment period (treatment difference vs placebo -3.5 mg/kg/min, P=0.0107). Total carbohydrate intake (enteral + parenteral) was lower with DASI treatment (treatment difference vs placebo -31 g/day, P=0.024), ~22% reduction in carbohydrate calories. No serious adverse events were reported and DASI was safe and well tolerated in study Part 1.

Conclusions: Dasiglucagon significantly reduces the requirement for intravenous glucose to maintain glycemia in neonates and infants with CHI and reduces glucose requirements to levels that potentially allow for discontinuation of IV glucose support. Dasiglucagon has the potential to be an effective, safe, and well tolerated novel treatment for newborns with CHI.