Endocrine Abstracts

JOINT1036

Background/Objectives: Congenital hyperinsulinism(CHI) is the most common cause of severe recurrent hypoglycemia in children. Early treatment is necessary to limit the risk of neurologic/developmental sequelae. Dasiglucagon is a glucagon analog suitable for continuous subcutaneous infusion shown to raise blood-glucose in a dose dependent manner. A 2-part phase 3 trial evaluated the efficacy/safety of dasiglucagon as add-on to standard-of-care(SoC) in children with CHI ages ≥3 months-<12 years with persistent hypoglycemia comparing dasiglucagon+SoC vs SoC only. The trial reported lower rates of SMPG-detected hypoglycemia in both groups compared to baseline, w/o statistically significant difference, but clinically meaningful reductions in all CGM-recorded measures of hypoglycemia for dasiglucagon+SoC (post-hoc analyses). Dasiglucagon was well tolerated with a safety profile in line with class effects of glucagon. Evaluation of effect on CGM percent time in hypoglycemia<70 mg/dL for consistency across different subgroups is presented here.

Methods: Evaluation of CGM percent time in hypoglycemia<70 mg/dL across subgroups was performed for the controlled part of the trial comparing dasiglucagon+SoC vs SoC. The statistical analysis model was the same as that applied in the original trial, a generalized linear regression model with normal distribution and log link function with the addition of the categorical subgroup variable and an interaction term between treatment group and the specific subgroup variable.

Results: Table displays treatment ratios for CGM percent time in hypoglycemia<70 mg/dL by subgroup. Overall effects were consistently in favor of dasiglucagon based on point-estimates for all subgroups, except for the age group of 6-12years, where there was only 1 patient in this group on dasiglucagon. Interaction P-values were low for some subgroups.

Conclusions: Dasiglucagon treatment in children with CHI has reported clinically meaningful reductions in CGM-recorded measures of hypoglycemia. Subgroup analysis for CGM-percent-time in hypoglycemia<70mg/dL supports consistent efficacy across subgroups. Due to the small size of the subgroups, results should be interpreted with caution. These data support the efficacy and safety of dasiglucagon as a potential novel therapy for CHI.