ESPE Yearbook of Paediatric Endocrinology

Brief Summary: This open-label, randomised phase 3 trial investigated the efficacy and safety of subcutaneous infusions of Dasiglucagon¹, a glucagon analogue, as an add-on to standard of care (SoC) treatment in infants and children with congenital hyperinsulinism (CHI).

Patients had documented CHI aged 0.6 to 10.9y, who had ≥3 episodes of hypoglycemia/week, defined as self-measured plasma glucose (SMPG) <3.9 mmol/L. Part 1 (weeks 1-4) randomised 32 children to receive either Dasiglucagon (step-up protocol, 10 to max 70 mcg/h; mean 30-35 mcg/) combined with SoC or SoC alone, and the primary outcome was (average number of SMPG values <3.9 mmol/L). During Part 2 (weeks 4-8) all chilren received SoC + Dasiglucagon. Demographic and baseline characteristics were comparable, with a mean age of 4.3 y (SD 2.8) and a balanced gender distribution; 66% had a gastrostomy and 34% had gone to surgery.

Dasiglucagon did not meet the primary endpoint (mean difference: 0.85 episodes per week, P=0.5). However, patients on Dasiglucagon had a 25% more weekly SMPG readings, suggesting more active self-monitoring. Post hoc analyses revealed a 43% reduction in CGM-detected hypoglycemia episodes on Dasiglucagon compared to SoC alone, and mean total gCHO intake was lower or decreased in children receiving Dasiglucagon (in Part 1 or Part 2).

More treatment-emergent adverse events (TEAEs) were reported on Dasiglucagon, most commonly infections, gastrointestinal disorders, and skin-related issues. Notably, hyperglycemia was reported in one patient, leading to the premature discontinuation of Dasiglucagon. Six serious, non-treatment-related events were reported.

Many drugs used to treat CHI do not have formal approval, and/or have limited effectiveness depending on CHI etiology and/or have concerning side effects. While the primary endpoint was not met, the findings provide valuable insights into the management of CHI and benefits for patient engagement. Dasiglucagon may not be sufficient as a standalone treatment, but it did allow for significant reductions in gCHO intake. In conclusion, the Dasiglucagon trial represents a significant step forward in understanding the treatment landscape for CHI.

References: 1. Hawkes C, De Leon D, Rickels M. Novel Preparations of Glucagon for the Prevention and Treatment of Hypoglycemia. Curr Diab Rep. 2020; 19: 97. doi: 10.1007/s11892-019-1216-4.