ESPE Abstracts

Congenital hyperinsulinism (CHI) is an ultra-rare disease characterized by excessive insulin secretion that results in persistent hypoglycemia. If left untreated, CHI-induced severe prolonged hypoglycemia may lead to permanent neurologic damage. Currently used pharmacologic agents fail to prevent hypoglycemia in a subset of patients with CHI. HM15136 is a novel long-acting glucagon analogue that have demonstrated good stability and extended half-life ranging from 77 to 167 hours, which is significantly greater than that of native glucagon (< 1 hour). The safety and tolerability of HM15136 along with dose dependent glucose escalation properties were demonstrated in Phase 1 studies. Based on its profile, we hypothesized that HM15136 can prevent hypoglycemia in subjects with CHI aged ≥2 years, who have persistent hypoglycemia while being on standard of care treatment. We have planned a multicentered Phase 2 study at centers of United States, United Kingdom, and Germany including the centers of excellence which provide the highest quality of care for CHI patients, which will be run from 2021 to 2024. In this study, 0.04 and 0.06 mg/Kg weekly doses of HM15136 will be tested for 8 weeks in children 2-11 years old (n=5 per dose) and in children and adults ≥12 years old (n=3 per dose). Because HM15136 was never evaluated among the subject with CHI and pediatric population before, step down approach is chosen for evaluating safety profile of HM15136 in subjects with CHI aged ≥12 years old first, though unmet needs are much higher among the children 2-11 years old. Dosing will be initiated in adolescents and adults at 0.04 mg/Kg. After review of safety/efficacy profile during 8-week treatment period, dose will be escalated to 0.06 mg/Kg in adolescents and adults, and younger children cohort will be initiated in parallel with dose of safety confirmed 0.04 mg/Kg. The dose escalation to 0.06 mg/Kg in children cohort will be decided by another safety/efficacy review. The primary endpoints will be safety, tolerability, and pharmacokinetics of HM15136. The secondary endpoint, an efficacy outcome, will be reduction of weekly hypoglycemia events measured by 7-point self-monitored blood glucose compared to the baseline. This Phase 2 study will provide important information about the safety, tolerability and efficacy of HM15136 for the development of a study design in neonates and infants and longer term Phase 3 studies in children with severe hypoglycemia due to CHI.