384-P: An Integrated Summary of Safety and Efficacy of a Ready-to-Use Liquid Glucagon Rescue Pen for the Treatment of Severe Hypoglycemia in Adults

Objective: To prevent medical complications of severe hypoglycemic emergencies, prompt and reliable rescue intervention is critically important. A ready-to-use stable liquid Glucagon Rescue Pen (GRP; Xeris Pharmaceuticals) auto-injector was evaluated for the rescue treatment of severe hypoglycemia. Method: Two Phase 3 randomized, controlled, blinded, crossover studies were conducted in 161 adults with T1D to compare 1 mg doses of GRP versus Glucagon Emergency Kit (GEK; Eli Lilly) for the treatment of insulin-induced severe hypoglycemia. Efficacy was evaluated as either a return of plasma glucose (PG) to >70 mg/dL or increase in PG ≥20 mg/dL from a baseline PG <50 mg/dL, within 30 min of dosing. Result: Subjects treated with GRP (98.7%) achieved successful PG recovery within 30 minutes, and (99.4%) had a PG > 70 mg/dL or neuroglycopenic symptom relief within 30 minutes, both comparable to GEK. From glucagon dosing, the mean time to achieve PG >70 mg/dL or increase in PG ≥20 mg/dL was 13.8±5.6 min for GRP and 10.0±3.6 min for GEK. This mean time does not account for the significantly shorter (p<0.0001) drug preparation and administration time for GRP (27.3±19.7 seconds) vs. GEK (97.2±45.1 seconds). The GRP was similar to GEK in terms of glucose Cmax, Tmax, and AUC(0-90min). The overall incidence of treatment emergent adverse events (TEAEs) was comparable in both groups; the most commonly reported TEAEs were nausea (GRP 29.9%, GEK 22.9%) and vomiting (GRP 16.1%, GEK 9.6%). One SAE was reported in these studies (GEK). Conclusion: A ready-to-use, easy two-step administration GRP achieved plasma glucose recovery reliably, was therapeutically equivalent to GEK, and had an incidence of nausea and vomiting comparable to GEK. There was a significant difference in drug preparation time in favor of the GRP. These results demonstrate that GRP is an effective, safe, and well tolerated rescue treatment for severe hypoglycemia and is a viable alternative to GEK. Disclosure M.P. Christiansen: Research Support; Self; Abbott, Biolinq, Dexcom, Inc., Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Medtronic MiniMed, Inc., Novo Nordisk A/S, Sanofi-Aventis, Xeris Pharmaceuticals, Inc. M.J. Cummins: Employee; Self; Xeris Pharmaceuticals, Inc. S.J. Prestrelski: Employee; Self; Xeris Pharmaceuticals, Inc. M.K. Junaidi: None.