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Dasiglucagon Hypopal® Autoinjector As a Fast and Effective Treatment for Severe Hypoglycemia: Results of a Phase 3 Trial

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Dasiglucagon Hypopal® Autoinjector As a Fast and Effective Treatment for Severe Hypoglycemia: Results of a Phase 3 Trial 2020 Dasiglucagon HypoPal® Autoinjector as a Fast and Effective Treatment for Severe Hypoglycemia: Results of a Phase 3 Trial Timothy S Bailey1, Julie Willard2, Leslie Klaff3, Lena S. List4, Anita E. Melgaard4 and Ramin Tehranchi4 1Escondido, CA, USA; 2Chula Vista, CA, USA; 3Renton, WA, USA; 4Copenhagen, Denmark LSL, AEM, and RT are employees of Zealand Pharma, the manufacturer of dasiglucagon and the sponsor of this clinical trial. 1 Timothy S. Bailey Disclosure • President & CEO, AMCR Institute, Escondido, CA, USA • Research Support: Abbott, Capillary Biomedical , Dexcom, Diasome, Eli Lilly, Kowa, Lexicon, Medtronic, Medtrum, Novo Nordisk, REMD, Sanofi, Senseonics, Viacyte, vTv Therapeutics, Zealand Pharma • Advisory Panel/Consultant: Abbott, Lifescan, Novo, Sanofi • Speaker: Medtronic, Sanofi • Stock/Shareholder: (none) 2 Introduction • Glucagon is a critical rescue medication to treat severe hypoglycemia in people with insulin-treated diabetes1,2 • However, glucagon is under-prescribed and proper training on its use is not adequate. This results in under-utilization of glucagon kits to treat or prevent severe hypoglycemia1-4 • Furthermore, glucagon injection kits require user training and multiple preparation steps. These are barriers to their prescription and effective utilization, especially under emergent circumstances1,2 1. Harris G. Pract Diabetes Int. 2001;18(1):22-25 2. Kedia N. Diabetes Metab Syndr Obes. 2011;4:337-346 3. Mitchell BD, et al. Endocr Pract. 2016;22:123-135 4. Haymond MW, et al. Clin Diabetes. 2019;37:162-166 3 Dasiglucagon for Severe Hypoglycemia Dasiglucagon* Rescue Pen • Specific glucagon-receptor agonist • Ready-to-use formulation • 7 amino acid substitutions to native • Easy-to-use, auto-injector glucagon administration • Physically and chemically stable in • Dual-storage conditions aqueous solution (refrigerated and room temperature) Aib A R A E E F K V W E S L T HSQGTFTSDYSKYLD Substitution Hot-spots For illustration only Hövelmann U, et al. Diabetes Care. 2018;41:531-537. *Investigational product, not FDA approved 4 Dasiglucagon HypoPal® Auto-Injector Phase 3 Trial Design Study of dasiglucagon versus placebo for treatment of insulin-induced hypoglycemia in T1DM* Randomization Dosing Dasiglucagon 0.6 mg (n = 34) Participants T1DM; insulin ≥ 1 year; 4-week safety HbA1c < 10%; follow-up Age: ≥ 18 y to ≤ 70 y (N = 45**) Induction Hypoglycemia Hypoglycemia Placebo (n = 10) 0 5 10 15 20 25 30 35 40 45 50 60 75 90 Minutes From Injection *NCT03688711: A randomized, double-blind, parallel-group trial to confirm the clinical efficacy and safety of dasiglucagon in the rescue treatment of hypoglycemia in subjects with type 1 diabetes mellitus (T1DM) compared to placebo. ** One participant was randomized to placebo but withdrew prior to trial treatment 5 Study Endpoints and Baseline Characteristics • Primary Endpoint Baseline Characteristics – Time to plasma glucose Dasiglucagon Placebo Total recovery defined as first (n=34) (n=10) (N=44) increase in plasma glucose of ≥ 20 mg/dL from time of Age (Years) 42.4 (13.5) 36.5 (12.8) 41.0 (13.4) injection* BMI (Kg/m2) 28.4 (5.8) 27.9 (4.0) 28.3 (5.4) Female, n (%) 18 (53%) 1 (10%) 19 (43%) ** • Secondary Endpoints HbA1c (%) 7.2 (5.8-9.6) 7.0 (6.1-8.8) 7.1 (5.8-9.6) – Plasma glucose recovery Diabetes (years) 22.5 (13.8) 21.2 (13.4) 22.2 (13.6) within 10, 15, 20, and 30 minutes from time of injection* Values for age, BMI and years with diabetes are presented as mean (SD) Values for HbA1c are presented as median (range) – Plasma glucose change from baseline at 10, 15, 20, and 30 minutes from time of injection* *Without administration of rescue intravenous glucose **Multiplicity adjusted 6 All Primary and Secondary Endpoints Met Dasiglucagon Placebo Dasiglucagon (n = 34) (n = 10) vs Placebo Median Time to plasma glucose recovery 10 (8, 12) 35 (20, -) P < 0.0001 (minutes) (95%CI) Participants with Plasma Glucose Increase Increase in Plasma Glucose from Baseline** ≥20 mg/dL** 97 100 94 * 100 88 90 90 85 80 80 Dasiglucagon 70 62 70 60 60 50 53 Placebo 50 50 42 40 40 Percentage patients of Percentage 30 30 25 20 20 15 10 10 10 10 5 0 0 (mg/dL) glucose in Plasma Increase 1 0 0 10 mins 15 mins 20 mins 30 mins 10 mins 15 mins 20 mins 30 mins *All participants treated with dasiglucagon achieved treatment success, except a single patient who received rescue glucose at 10 min, per protocol **p-values for comparison versus placebo statistically significant at all timepoints (≤ 0.001) 7 Plasma Glucose Increased Rapidly and Consistently with Dasiglucagon Mean Increase in Plasma Glucose from Baseline (mg/dL) 120 Dasiglucagon 0.6 mg e s a e 100 Placebo r c n I 80 ) e L s d / o 60 c g u l m Median Exact Time to 20 mg/dL ( G 40 a Increase in Plasma Glucose m s 20 a Plasma Dasiglucagon Placebo l P 0 glucose (n = 34) (n = 10) recovery* 10 20 30 40 50 Time Post-dose (minutes) Median min 9.3 25.8 [95% CI] [7.8, 10.3] [19.2, 34.8] *Estimated true time 8 Summary of Treatment-Emergent Adverse Events Dasiglucagon 0.6 mg Placebo Treatment-Emergent Adverse Events (TEAE) (n = 34) (n = 10) All TEAE 24 (70.6%) 3 (30.0%) Serious TEAE 0 0 Severe TEAE* 2 (5.9%) 0 Most Frequent drug-related TEAE (≥ 10% of patients)** Nausea*** 21 (61.8%) 1 (10%) Vomiting*** 10 (29.4%) 0 TEAE Leading to Discontinuation 0 0 * One participant with severe hypoglycemia and another with nausea ** Drug-related TEAE was defined as any TEAE classified as possible and probable *** The majority of these events were evaluated as possibly or probably related to treatment page 9 9 Conclusions • Dasiglucagon HypoPal® Autoinjector is a fast and effective treatment for severe hypoglycemia • All primary and secondary endpoints were met ✓ Median time to plasma glucose recovery was 10 min with dasiglucagon versus 35 minutes with placebo • Generally safe and well-tolerated • Results consistent with prior pivotal phase 3 trial evaluating dasiglucagon administered via a pre-filled syringe.
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