Data from phase III trial of dasiglucagon in congenital hyperinsulinism are presented at the 60th Annual ESPE Meeting

Topline results from Part 1 of the trial were previously announced in May 2022 (Company Announcement No. 22 / 2022).

“Children with CHI can experience significant and permanent neurologic complications as a result of hypoglycemia, and many infants are dependent on intravenous glucose, and in some cases require pancreatectomy, to maintain euglycemia. I am encouraged by the results from Part 1 of this Phase III study demonstrating that dasiglucagon treatment resulted in a significant reduction in glucose infusion rate, and to see this trend continue in Part 2, in which the majority of infants could reduce or in many cases be weaned off of IV glucose infusion and also avoid pancreatectomy,” said Diva D. De León-Crutchlow, M.D., M.S.C.E., Chief of the Division of Endocrinology and Diabetes and Director of the Congenital Hyperinsulinism Center at Children's Hospital of Philadelphia and a study principal investigator. “Though congenital hyperinsulinism is an incredibly challenging disease to manage, the efficacy and safety of dasiglucagon observed in this Phase III trial, support its potential as a new treatment option for children with CHI.”

The abstracts of the oral presentations are available at eurospe.org and the data are summarized as follows;

1. Title: "Dasiglucagon Significantly Reduces Requirement for Intravenous Glucose in Children with Congenital Hyperinsulinism ages 7 Days to 12 Months"-Authors: Diva D. De Leon, Indraneel Banerjee, David M. Kendall, Sune Birch, Eva Bøge, Jelena Ivkovic & Paul S. Thornton. Presentation Highlights: In Part 1 of the Phase III trial, dasiglucagon significantly reduced the requirement for intravenous (IV) glucose to maintain glycemia in neonates and infants with CHI and reduced glucose requirements to levels that potentially allow for discontinuation of IV glucose support. i. Dasiglucagon significantly reduced the mean IV glucose infusion rate (GIR) in the last 12 hours of the 48 hour treatment period by 55% as compared to placebo (4.3 mg/kg/min for dasiglucagon and 9.4 mg/kg/min for placebo with a treatment difference of 5.2 mg/kg/min; p=0.0037). ii. Dasiglucagon also reduced GIR over the entire 48-hour treatment period by 3.5 mg/kg/min compared to placebo (p=0.0107). iii. Dasiglucagon treatment resulted in a reduction of 31 g/day in total carbohydrate intake (IV and gastric) compared to placebo (107 g/day for dasiglucagon vs 138 g/day for placebo; p = 0.024), a 22% reduction in carbohydrate calories.iv. Dasiglucagon was observed to be well tolerated in Part 1 of the trial, with skin reactions and gastrointestinal disturbances as the most frequently reported adverse events (no serious adverse events reported).

2. Title: "Dasiglucagon Treatment Over 21 days in Infants with Congenital Hyperinsulinism Results in Glycaemic Stability and Reduces Requirement for Intravenous Glucose"; Authors: Indraneel Banerjee, Diva D. De Leon, David M. Kendall, Sune Birch, Eva Bøge, Jelena Ivkovic & Paul S. Thornton. Presentation Highlights: In the 21-day open-label Part 2 of the Phase III trial, continuous subcutaneous infusion of dasiglucagon in infants with CHI reduced IV glucose requirements, time in hypoglycaemia and enabled discontinuation of IV glucose in most infants, obviating the need for subtotal pancreatectomy for glycaemic stability. i.Dasiglucagon enabled reduction and either periodic or permanent discontinuation of IV glucose infusion in 10 out of 12 infants. ii. Seven infants, who did not require pancreatectomy, were completely weaned off IV glucose at the completion of the trial. iii. During the 21-day treatment with dasiglucagon, continuous glucose monitoring (CGM) measures of hypoglycaemia trended lower with median time <70 mg dl reduced from 7.0% to 5.2% and><54 mg dl reduced from 1.9% to 0.88%. there was no increase in hyperglycaemia. iv. the safety profile of dasiglucagon in part 2 was consistent with part 1, with no adverse event requiring discontinuation of treatment and no serious adverse events reported.

About the Phase III Trial The Phase III trial (17103) was designed to investigate the potential for chronic dasiglucagon infusion, delivered subcutaneously via a pump, to prevent hypoglycemia in newly diagnosed children with CHI who are dependent on intravenous glucose. The trial was conducted in two parts. Part 1 was a double-blind, placebo-controlled two-period crossover with treatment periods of 48 hours each. Part 2 was an open-label, single-arm study of dasiglucagon treatment for an additional 21 days. The primary objective of the overall trial was to reduce or eliminate the need for intensive hospital treatment, reduce the frequency of dangerously low blood glucose (hypoglycemia) and the need for constant feeding, and to potentially delay or eliminate the need for pancreatectomy. (ClinicalTrials.gov: NCT04172441).