ESPE Abstracts

Background: Congenital hyperinsulinism (CHI) is a rare disease affecting neonates, infants, and children caused by dysregulated insulin secretion resulting in severe recurrent hypoglycemia. Early treatment is necessary to limit the risk of neurologic and developmental sequelae. Dasiglucagon is a glucagon analog (stable liquid formulation) suitable for continuous subcutaneous infusion shown to raise blood glucose in a dose-dependent manner. Results from a 2-part phase 2/3 trial evaluating the efficacy and safety of dasiglucagon in 12 children with CHI ages ≥7 days and <12 months of age with intravenous glucose requirements ≥ 10 mg/kg/min reported significantly reduced IV glucose requirements (primary endpoint) and total carbohydrate intake vs placebo. Dasiglucagon was well tolerated with a safety profile in line with class effects of glucagon. Evaluation of efficacy and safety across different subgroups for consistency is presented.

Methods: An evaluation of IV glucose infusion rate (GIR) across subgroups was performed on the primary endpoint from the placebo-controlled part 1 of the trial. The subgroups were derived from baseline demographics and treatment characteristics. The statistical analysis model was the same as that applied in the original trial with the addition of the categorical subgroup variable and an interaction term between treatment group and the specific subgroup variable. Furthermore, TEAEs by subgroup were evaluated.

Results: Effects on weighted mean IV GIR were consistently in favor of dasiglucagon based on point estimates for 20 of 21 subgroups. There was no indication of different effects in subgroups based on subgroup interaction p-values for all subgroups, except genetic analysis. The test for treatment by genetic subgroup interaction revealed a low p-value, however there were only 2 patients in the subgroup with no CHI mutations. The observed treatment differences showed one patient had a small increase in IV GIR with dasiglucagon (approx. +0.5 mg/kg/min) while another had a small decrease close to the overall mean (approx. 4.1 mg/kg/min). Regarding safety there was no indication that the number of adverse events differs between subgroups.

Conclusion: As previously reported dasiglucagon treatment in infants with CHI significantly reduced IV glucose requirements and total carbohydrate intake during a phase 2/3 trial. Subgroup analysis for the primary endpoint supports consistent efficacy across subgroups with no indication of different frequencies of adverse events among subgroups. Results should be interpreted with caution due to the small size of the subgroups. These data support the efficacy and safety of dasiglucagon as a potential novel therapy for CHI.