SAT-272 A Phase 2 Comparison of a Stable Liquid Glucagon to Placebo for the Treatment of Congenital Hyperinsulinism

Abstract

OBJECTIVE: A novel ready-to-use stable liquid Glucagon (CSIG; Xeris Pharmaceuticals) delivered continuously through a patch pump, was evaluated for the treatment of congenital hyperinsulinism (CHI). METHOD: This was a Phase 2, randomized, placebo-controlled, double-blind trial with open-label follow-up designed to assess the efficacy of CSIG to prevent hypoglycemia and lower intravenous glucose infusion rates (GIR), in subjects < 1 year of age with CHI. CSIG (5-20 μg/kg/hr) or matching placebo was delivered through a patch pump (Omnipod®; Insulet) as a continuous subcutaneous infusion, after the minimum GIR necessary to maintain euglycemia was established. Subjects did not receive other CHI-related medications. The study consisted of a baseline GIR stabilization phase (Period 1), a double-blind placebo-control parallel phase (Period 2), and an open-label CSIG single-arm active phase (Period 3). A positive clinical response was defined as a 33% reduction in GIR after 48 hours of study drug treatment. RESULT: A total of five subjects were screened for inclusion and enrolled in the study (intent-to-treat). The first enrolled subject’s medical history indicated a significant treatment resistance to reconstituted IV glucagon, in a previous CHI treatment session. The remaining 4 subjects were considered fully evaluable for clinical response (per-protocol). In Period 1, all subjects were able to obtain a stable GIR (range: 5.9 to 28.6 mg/kg/min). In Period 2, subjects assigned to blinded placebo had a GIR response that ranged from a 31% reduction to a 34% increase, while subjects assigned to blinded CSIG experienced GIR reductions of 53%-65%. In Period 3, the 4 evaluable subjects who received open label CSIG achieved reductions of 44%-66%, relative to baseline GIR. Total treatment time with CSIG in the study ranged from 4-72 hours. As a sole therapy during the blinded phase, treated subjects had a positive clinical response when administered CSIG treatment (2/2), compared to subjects given placebo (0/2). Open-label treatment resulted in a clinically meaningful GIR response in all evaluable subjects (4/4). There were no reported serious adverse events, no skin reactions, and no other negative treatment effects associated with study drug administration. Furthermore, there were no reports of occlusions, leakage or other pump issues in the study, or any instances of severe hypoglycemia during pump change-out. CONCLUSION: Glucose supplementation to prevent severe hypoglycemia and neurologic injury is critical in CHI. Reducing GIR while maintaining euglycemia reduces IV glucose-related complications in the management of CHI. As a sole therapy, CSIG achieved successful GIR reduction in a reliable manner, was safe and well tolerated. These results demonstrate that CSIG is a promising therapy in the treatment of CHI.