Zegalogue (dasiglucagon) / Zealand Pharma, Novo Nordisk - LARVOL DELTA

Managing post-bariatric hypoglycemia: a systematic review of pharmacological therapies. (PubMed, Diabetol Metab Syndr) - "Pharmacologic management of PBH shows promise with agents such as anakinra, empagliflozin, pasireotide, and acarbose. However, given the considerable heterogeneity, small sample sizes, and wide confidence intervals, very low quality of effect estimates, and varied definitions of PBH, these pooled estimates should be considered hypothesis-generating only, and not confirmatory. There is an urgent need for standardized PBH definitions, patient-centered outcome measures, longer follow-up, and adequately powered RCTs to establish evidence-based therapeutic guidelines."

Clinical • Journal • Hypoglycemia

NN9515-7675: Research Study in Japan to Compare Dasiglucagon With Glucagon in Treating Very Low Levels of Blood Sugar in Asian Adults With Type 1 Diabetes and Testing of Dasiglucagon for the Same Condition in Japanese Adolescents (clinicaltrials.gov) - P1 | N=38 | Completed | Sponsor: Novo Nordisk A/S | Recruiting ➔ Completed

Trial completion • Diabetes • Metabolic Disorders • Severe Hypoglycemia • Type 1 Diabetes Mellitus

A Study to Inv. Safety, Efficacy & PD of Dasiglucagon as Hypoglycemia Rescue Therapy in Children <6 Years With T1D (clinicaltrials.gov) - P3 | N=8 | Completed | Sponsor: Zealand Pharma | Recruiting ➔ Completed

Trial completion • Diabetes • Metabolic Disorders • Pediatrics • Severe Hypoglycemia • Type 1 Diabetes Mellitus

Extension Trial Evaluating the Long-term Safety and Efficacy of Dasiglucagon in Children With Congenital Hyperinsulinism (clinicaltrials.gov) - P3 | N=44 | Active, not recruiting | Sponsor: Zealand Pharma | Trial completion date: Jan 2025 ➔ Dec 2026

Trial completion date

A Study to Inv. Safety, Efficacy & PD of Dasiglucagon as Hypoglycemia Rescue Therapy in Children <6 Years With T1D (clinicaltrialsregister.eu) - P3 | N=8 | Sponsor: Zealand Pharma A/S

New P3 trial • Diabetes • Metabolic Disorders • Pediatrics • Severe Hypoglycemia • Type 1 Diabetes Mellitus

Upcoming events next 12 months (GlobeNewswire) - "In the second half of 2025, Zealand Pharma expects to submit a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) and initiate a Phase 3 clinical trial of glepaglutide (EASE-5) that is anticipated to provide further confirmatory evidence for a regulatory submission in the U.S. and to support regulatory submissions outside the U.S. and the EU. In parallel, the company is engaging in partnership discussions for future commercialization...Zealand Pharma is ready to resubmit the New Drug Application for dasiglucagon for up to three weeks of dosing and to submit the requested analyses from existing continuous glucose monitoring datasets to support use beyond three weeks...In parallel, the company is engaging in partnership discussions for future commercialization....Zealand Pharma expects to complete the first-in-human clinical trial with ZP9830 in the fourth quarter of 2025 and report topline data in the first half of 2026."

EMA filing • FDA filing • New P3 trial • P1 data • Immunology • Rare Diseases • Short Bowel Syndrome

Necrolytic migratory erythema following prolonged continuous subcutaneous Dasiglucagon administration: a case report (ESPE-ESE 2025) - "Monitoring should prioritize the early identification of potential adverse effects, including dermatological conditions, amino acid and zinc deficiencies, and alterations in weight trajectory. Although this case report does not establish a direct causal relationship between continuous dasiglucagon therapy and NME, it emphasizes the need for vigilant long-term use, multidisciplinary care, and further research to enhance the understanding of its safety profile and optimize therapeutic strategies."

Case report • Clinical • Dermatology • Diabetes • Infectious Disease • Metabolic Disorders • Septic Shock • Severe Hypoglycemia

Dasiglucagon Treatment Consistently Reduces Hypoglycemia assessed by Continuous Glucose Monitoring in Children with Congenital Hyperinsulinism across Subgroups (ESPE-ESE 2025) - "Dasiglucagon treatment in children with CHI has reported clinically meaningful reductions in CGM- recorded measures of hypoglycemia. Subgroup analysis for CGM-percent-time in hypoglycemia<70mg/dL supports consistent efficacy across subgroups. Due to the small size of the subgroups, results should be interpreted with caution."

Clinical • Hypoglycemia

Necrolytic migratory erythema following prolonged continuous subcutaneous dasiglucagon administration: a rare dermatologic adverse event. (PubMed, Endocrinol Diabetes Metab Case Rep) - "Close monitoring is essential during prolonged continuous subcutaneous dasiglucagon therapy to detect potential adverse effects, focusing on dermatological conditions, nutrient deficiencies or signs of infection. Multidisciplinary care is crucial to manage CHI with dasiglucagon, ensuring a comprehensive approach that addresses both glycemic control and potential side effects."

Adverse events • Journal • Dermatology • Hypoglycemia • Infectious Disease • Septic Shock

Highlights of the year and key events anticipated in 2025 (GlobeNewswire) - "Zealand Pharma is prepared to resubmit the New Drug Application (NDA) for three weeks of dosing to the U.S. FDA contingent on the third-party manufacturing facility receiving an inspection classification upgrade. Subsequently, Zealand Pharma also expects to submit the required and detailed analyses from existing continuous glucose monitoring datasets to support the use of dasiglucagon beyond three weeks....In 2025, the company expects to initiate a single placebo-controlled Phase 3 trial (EASE-5) to provide further confirmatory evidence for a regulatory submission in the U.S. and to support regulatory submissions for glepaglutide in geographies outside the U.S. and the EU. In parallel, Zealand Pharma anticipates proceeding with current plans to submit a Marketing Authorization Application to support EU approval."

EMA filing • FDA filing • New P3 trial • Rare Diseases • Short Bowel Syndrome

Response to Letter to the Editor from He et al.: "Dasiglucagon in Children with Congenital Hyperinsulinism up to 1 Year of Age: Results from a Randomized Clinical Trial". (PubMed, J Clin Endocrinol Metab) - No abstract available

Clinical • Journal • Hypoglycemia

Letter to the Editor From He et al.: "Dasiglucagon in Children with Congenital Hyperinsulinism up to 1 Year of Age: Results from a Randomized Clinical Trial". (PubMed, J Clin Endocrinol Metab) - No abstract available

Clinical • Journal

Dasiglucagon in Children with Congenital Hyperinsulinism up to 1 Year of Age: Results from a Randomized Clinical Trial. (PubMed, J Clin Endocrinol Metab) - "In infants with CHI, dasiglucagon significantly reduced the amount of IV glucose needed to maintain euglycemia compared with placebo. Dasiglucagon represents a promising treatment for the management of CHI."

Clinical • Journal • Dermatology • Gastrointestinal Disorder • Hypoglycemia

ABCC8 gene mutations: two mirror reflections (ESPE 2024) - "Oral glibenclamide was never started in an outpatient setting due to the difficulty of dispensing minimal doses to a remote distance...Due to moderate hepatic steatosis, therapy with dasiglucagon is being considered...In ND sulphonylureas provide an effective treatment in most cases and transient forms may require a continuous adaptation to progressive reduction of insulin and glibencalmide dosing. On the other hand, management of CHI represents a greater therapeutic challenge, typically in diffuse cases unresponsive to diazoxide, often requiring somatostatin analogs or even partial pancreatic resection."

Late-breaking abstract • Diabetes • Gastroenterology • Gastrointestinal Disorder • Hypoglycemia • Metabolic Disorders

Efficacy and Safety across Subgroups in Children with Congenital Hyperinsulinism Treated with Dasiglucagon (ESPE 2024) - "As previously reported dasiglucagon treatment in infants with CHI significantly reduced IV glucose requirements and total carbohydrate intake during a phase 2/3 trial. Subgroup analysis for the primary endpoint supports consistent efficacy across subgroups with no indication of different frequencies of adverse events among subgroups. Results should be interpreted with caution due to the small size of the subgroups."

Clinical • Hypoglycemia • Rare Diseases

Dasiglucagon: a New Hope for Managing Post-prandial Hypoglycemia After Gastric Bypass Surgery? (PubMed, Obes Surg) - No abstract available

Bariatric surgery • Journal • Surgery • Hypoglycemia

NN9515-7675: Research Study in Japan to Compare Dasiglucagon With Glucagon in Treating Very Low Levels of Blood Sugar in Asian Adults With Type 1 Diabetes and Testing of Dasiglucagon for the Same Condition in Japanese Adolescents (clinicaltrials.gov) - P1 | N=38 | Recruiting | Sponsor: Novo Nordisk A/S | Not yet recruiting ➔ Recruiting

Enrollment open • Diabetes • Metabolic Disorders • Severe Hypoglycemia • Type 1 Diabetes Mellitus

Research Study in Japan to Compare Dasiglucagon With Glucagon in Treating Very Low Levels of Blood Sugar in Asian Adults With Type 1 Diabetes and Testing of Dasiglucagon for the Same Condition in Japanese Adolescents (clinicaltrials.gov) - P3 | N=38 | Not yet recruiting | Sponsor: Novo Nordisk A/S

New P3 trial • Diabetes • Metabolic Disorders • Severe Hypoglycemia • Type 1 Diabetes Mellitus

A Study to Inv. Safety, Efficacy & PD of Dasiglucagon as Hypoglycemia Rescue Therapy in Children <6 Years With T1D (clinicaltrials.gov) - P3 | N=8 | Recruiting | Sponsor: Zealand Pharma | Trial primary completion date: Mar 2024 ➔ Sep 2024

Trial primary completion date • Diabetes • Metabolic Disorders • Pediatrics • Severe Hypoglycemia • Type 1 Diabetes Mellitus

Hypoglycemia and Alzheimer Disease Risk: The Possible Role of Dasiglucagon. (PubMed, Cell Mol Neurobiol) - "A recent glucagon receptor agonist dasiglucagon which used in the management of hypoglycemia may be effective in preventing hypoglycemia and AD neuropathology. This review aims to discuss the potential role of dasiglucagon in treating hypoglycemia in AD, and how this drug reduce AD neuropathology."

Journal • Review • Alzheimer's Disease • Cardiovascular • CNS Disorders • Cognitive Disorders • Dementia • Diabetes • Hematological Disorders • Hypoglycemia • Metabolic Disorders • Thrombosis • Type 2 Diabetes Mellitus

Zealand Pharma Announces Financial Results for the First Quarter of 2024 (GlobeNewswire) - "Dasiglucagon (CHI): US FDA has granted a PDUFA date of October 8, 2024 for dasiglucagon in CHI for up to three weeks of dosing (Part 1 of NDA)...Submission of Part 2 of the NDA is moved into the second half of 2024."

NDA • PDUFA • Diabetes • Hypoglycemia • Metabolic Disorders

Budget Impact Model for Dasiglucagon in the Prevention and Treatment of Hypoglycemia in Pediatric Patients with Congenital Hyperinsulinism in the United States (ISPOR 2024) - "The de-novo BIM includes clinical data, costs, and published literature, accommodating uncertainty through sensitivity and scenario analyses. While the BIM does not account for dasiglucagon’s improved glycemic control, dasiglucagon is anticipated to expedite hospital discharge and lower resource utilization. Future cost-effectiveness analyses should encompass these outcomes."

Clinical • HEOR • CNS Disorders • Diabetes • Epilepsy • Hypoglycemia • Metabolic Disorders • Pediatrics • Rare Diseases • Type 1 Diabetes Mellitus • Vascular Neurology

Extension Trial Evaluating the Long-term Safety and Efficacy of Dasiglucagon in Children With Congenital Hyperinsulinism (clinicaltrials.gov) - P3 | N=44 | Active, not recruiting | Sponsor: Zealand Pharma | Trial completion date: Apr 2024 ➔ Jan 2025 | Trial primary completion date: Apr 2024 ➔ Jan 2025

Trial completion date • Trial primary completion date

Glucose-Driven Droplet Formation in Complexes of a Supramolecular Peptide and Therapeutic Protein. (PubMed, J Am Chem Soc) - "These droplets also offer function in mitigating the most severe effects of hypoglycemia arising from an insulin overdose through delivery of dasiglucagon in a mouse model of hypoglycemic rescue. Accordingly, this approach to use complexation between a supramolecular peptide amphiphile and a therapeutic protein in the presence of glucose leads to droplets with functional potential to dissipate for the release of the therapeutic material in low blood glucose environments."

Journal • Hypoglycemia

STABLE-1: A Stable Glucagon Analog Administered by a Bihormonal Closed Loop System (clinicaltrials.gov) - P2 | N=0 | Withdrawn | Sponsor: Inreda Diabetic B.V. | N=12 ➔ 0 | Trial completion date: Aug 2023 ➔ Dec 2023 | Not yet recruiting ➔ Withdrawn | Trial primary completion date: Jul 2023 ➔ Dec 2023

Enrollment change • Trial completion date • Trial primary completion date • Trial withdrawal • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus