efpegerglucagon (HM15136) / Hanmi - LARVOL DELTA

Treatment of Congenital Hyperinsulinism With a Novel, Long-acting Glucagon Analogue. (PubMed, JCEM Case Rep) - "She has continued treatment with efpegerglucagon through a single-patient Investigational New Drug Expanded Access Program and has demonstrated improved glycemic control throughout 10 months of treatment. Efpegerglucagon may be a viable treatment option or adjunct therapy for patients with HI who are unresponsive or partially responsive to currently available therapies."

Journal • CNS Disorders • Hypoglycemia • Rare Diseases • Vascular Neurology

An Ongoing Phase 2 Study of Efpegerglucagon: Promising Results on Safety and Efficacy in Subjects with Congenital Hyperinsulinism (ESPE-ESE 2025) - No abstract available

Clinical • P2 data

An Ongoing Phase 2 Study of Efpegerglucagon: Promising Results on Safety and Efficacy in Subjects with Congenital Hyperinsulinism (ESPE-ESE 2025) - "Efpegerglucagon demonstrated a favorable safety profile and clinically meaningful efficacy. After eight weeks of treatment, CHI patients experienced significant reductions in hypoglycemia events. These findings emphasize its therapeutic potential as a safe and effective treatment for CHI and support the continued enrollment of Cohort 2."

Clinical • P2 data • Diabetes • Gastrointestinal Disorder • Pain • Rare Diseases • Severe Hypoglycemia

HM15136 (efpegerglucagon) Treatment for 8 Weeks in Subjects Aged ≥2 Years with Congenital Hyperinsulinism (CHI) (clinicaltrials.gov) - P2 | N=16 | Recruiting | Sponsor: Hanmi Pharmaceutical Company Limited | Trial completion date: Mar 2025 ➔ Dec 2025 | Trial primary completion date: Mar 2025 ➔ Dec 2025

Trial completion date • Trial primary completion date

Safety and efficacy of efpegerglucagon in patients with congenital hyperinsulinism: interim results from a phase 2 study (ESPE 2024) - "After eight weeks of treatment with efpegerglucagon, patients with CHI demonstrated clinically significant reductions in hypoglycemia events. These findings, combined with favorable safety and tolerability profiles, strongly suggest its therapeutic potential as a safe and effective therapy for CHI patients."

Clinical • Late-breaking abstract • P2 data • Gastroenterology • Gastrointestinal Disorder • Hypoglycemia • Pain • Rare Diseases

GLUCAGON ENGAGEMENT IS ESSENTIAL FOR THE DIRECT ANTI-INFLAMMATION AND ANTI-FIBROSIS EFFECT OF EFOCIPEGTRUTIDE IN TAA-INDUCED MOUSE MODEL OF LIVER INJURY AND FIBROSIS (AASLD 2024) - "In TAA mice, efocipegtrutide (GCG/GIP/GLP-1 triple) and efpegerglucagon (GCG mono) showed similar anti-inflammatory and anti-fibrosis benefits while tirzepatide (GIP/GLP-1 dual) had relatively little effect. These result demonstrate that GCG engagement could play a crucial role in managing hepatic inflammation and fibrosis. P2b study in biopsy confirmed MASH patients is currently ongoing to assess the clinical relevance of these findings."

Preclinical • Fibrosis • Hepatology • Immunology • Inflammation • Liver Failure • Metabolic Dysfunction-Associated Steatohepatitis • GCG • TIMP1

In vitro characterization of a novel long-acting glucagon analog (HM15136) and its potential effect in animal models of chronic hypoglycemic diseases (ENDO 2023) - "Based on these results, HM15136 could be a potential therapeutic option for chronic hypoglycemic diseases including CHI and PBH. Phase 2 clinical study in CHI subjects is on-going to assess the clinical relevance of these findings."

Preclinical • Diabetes • Gastrointestinal Disorder • Genetic Disorders • Metabolic Disorders • Severe Hypoglycemia

Safety, tolerability, pharmacokinetics and pharmacodynamics of multiple ascending doses of the novel long-acting glucagon analogue HM15136 in overweight and obese patients with co-morbidities. (PubMed, Diabetes Obes Metab) - "This study of HM15136 provides a preliminary safety and tolerability profile with initial insights into its efficacy profile."

Journal • PK/PD data • Cardiovascular • Diabetes • Dyslipidemia • Hypertension • Hypoglycemia • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

An Ongoing Phase 2 Study of HM15136, a Novel Long-acting Glucagon Analogue, in Subjects with Congenital Hyperinsulinism (ACHIEVE, Outline Protocol) (ESPE 2022) - "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."

Clinical • P2 data • Pediatrics • Rare Diseases • Severe Hypoglycemia

A novel glucagon analog with an extended half-life, HM15136, normalizes glucose levels in rodent models of congenital hyperinsulinism. (PubMed, Sci Rep) - "Further, HM15136 could effectively reverse acute hypoglycemia induced by insulin challenge, and multiple doses of HM15136 could sustain increased blood glucose levels in CHI rats. In conclusion, our findings indicate that HM15136 promotes sustained elevation of blood glucose, demonstrating the potential for development as a once-weekly therapy for CHI."

Journal • Preclinical • Hypoglycemia

Beneficial effects on metabolic disorders by a long-acting glucagon analogue, HM15136, in pre-clinical models (EASD 2022) - "These results highlight that HM15136 could have therapeutic potential on not only obesity but also related complications especially renal disorders. Further studies are needed to assess a clinical relevance of these findings."

Preclinical • Metabolic Disorders • Obesity • TGFB1

HM15136 Treatment for 8 Weeks in Subjects Aged ≥2 Years With Congenital Hyperinsulinism (CHI) (clinicaltrials.gov) - P2 | N=16 | Recruiting | Sponsor: Hanmi Pharmaceutical Company Limited | Trial completion date: Apr 2023 ➔ Mar 2025 | Trial primary completion date: Dec 2022 ➔ Mar 2025

Trial completion date • Trial primary completion date

A Double-Blind, Placebo-Controlled Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of HM15136 in Obese or Overweight Subjects with Co-morbidities (ENDO 2022) - "These results suggest future development opportunities for the management of treatment requiring hypoglycemia. A phase 2, Proof-of-Concept study in patients with congenital hyperinsulinism is currently ongoing."

Clinical • PK/PD data • Genetic Disorders • Hypoglycemia • Metabolic Disorders • Obesity

HM15136 Treatment for 8 Weeks in Subjects Aged ≥2 Years With Congenital Hyperinsulinism (CHI) (clinicaltrials.gov) - P2 | N=16 | Recruiting | Sponsor: Hanmi Pharmaceutical Company Limited | Not yet recruiting ➔ Recruiting

Enrollment open

A double-blind, placebo-controlled single ascending dose study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of HM15136, a novel long-acting glucagon analogue, in healthy subjects. (PubMed, Diabetes Obes Metab) - "A single subcutaneous dose of HM15136 at 10-120 μg/kg was safe and well tolerated. The long half-life of HM15136, coupled with an increase in blood glucose for ~2 weeks, may warrant a weekly dosing regimen."

Clinical • Journal • PK/PD data

[VIRTUAL] Potential effect of a novel combination of GLP-1RA (efpeglenatide) and long-acting glucagon analogue (HM15136) in animal models of metabolic disorder (EASD 2021) - "HM15136 might be a novel COMBO partner for Efpe, providing enhanced BWL and favorable metabolic profiles. These results warrants further evaluation for therapeutic potential of this novel COMBO in various metabolic disorders including T2DM, dyslipidemia and NASH."

Preclinical • Metabolic Disorders • Non-alcoholic Steatohepatitis • Obesity • Type 2 Diabetes Mellitus

HM15136 Treatment for 8 Weeks in Subjects Aged ≥2 Years With Congenital Hyperinsulinism (CHI) (clinicaltrials.gov) - P2; N=16; Not yet recruiting; Sponsor: Hanmi Pharmaceutical Company Limited; Initiation date: Jun 2021 ➔ Oct 2021

Clinical • Trial initiation date

[VIRTUAL] Sustained Glucagon Effect on Cardiovascular Renal and Metabolic Disorders Mediated by a Long-Acting Glucagon Analog, HM15136, in Animal Disease Models (ADA 2021) - "Hence, mechanistic study results highlight the essential role of direct GCG engagement in improvement of cardiovascular renal and metabolic diseases. Further studies are needed to assess a clinical relevance of these findings."

Metabolic Disorders • Obesity

[VIRTUAL] Potential Effect of a Novel Combination of GLP-1RA (efpeglenatide) and Long-Acting Glucagon Analog (HM15136) in Animal Models of Metabolic Disorders (ADA 2021) - "Therefore, HM15136 might be a novel COMBO partner for Efpe, providing enhanced BWL and favorable metabolic profiles. These results warrants further evaluation for therapeutic potential of this novel COMBO in various metabolic disorders including dyslipidemia and NASH."

Preclinical • Metabolic Disorders • Non-alcoholic Steatohepatitis • Obesity

Study for Multiple Doses of HM15136 in Obese or Overweight Subjects With Comorbidities (clinicaltrials.gov) - P1; N=53; Completed; Sponsor: Hanmi Pharmaceutical Company Limited; Active, not recruiting ➔ Completed

Trial completion • Diabetes • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

HM15136 Treatment for 8 Weeks in Subjects Aged ≥2 Years With Congenital Hyperinsulinism (CHI) (clinicaltrials.gov) - P2; N=16; Not yet recruiting; Sponsor: Hanmi Pharmaceutical Company Limited

Clinical • New P2 trial

Study for Multiple Doses of HM15136 in Obese or Overweight Subjects With Comorbidities (clinicaltrials.gov) - P1; N=53; Active, not recruiting; Sponsor: Hanmi Pharmaceutical Company Limited; Recruiting ➔ Active, not recruiting; Trial completion date: Mar 2021 ➔ Dec 2021; Trial primary completion date: Mar 2021 ➔ Dec 2021

Clinical • Enrollment closed • Trial completion date • Trial primary completion date • Diabetes • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

[VIRTUAL] Multiple mechanisms of a novel long-acting glucagon analogue, HM15136, on weight loss in animal models of obesity (EASD 2020) - "Materials and For a BWL efficacy comparison between HM15136 and GLP-1RAs, either HM15136 or available GLP-1RAs (liraglutide, dulaglutide or semaglutide) were subcutaneously administered into DIO mice for 4 weeks. Based on these results, HM15136 could be a potential therapeutic option for the management of obesity via favorable regulation of energy expenditure and lipid absorption in addition to appetite inhibition. Efficacy study of HM15136 in obese patients is ongoing to assess the clinical relevance of these findings."

Preclinical • Metabolic Disorders • Obesity • APOB

[VIRTUAL] Beneficial effects of a novel long-acting glucagon analogue, HM15136, on obesity and obesity related metabolic disorders in animal models (EASD 2020) - "To our knowledge, this is the first study demonstrating the potential benefits of chronic GCG engagement in the management of body weight, blood lipid, and even BG. Based on these results, HM15136 might be a novel therapeutic option for the management of obesity and related metabolic disorders. Human study of HM15136 is ongoing for the clinical relevance of these findings."

Preclinical • Diabetes • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Study for Multiple Doses of HM15136 in Obese or Overweight Subjects With Comorbidities (clinicaltrials.gov) - P1; N=72; Recruiting; Sponsor: Hanmi Pharmaceutical Company Limited; Trial completion date: Dec 2020 ➔ Mar 2021; Trial primary completion date: Dec 2020 ➔ Mar 2021

Clinical • Trial completion date • Trial primary completion date • Diabetes • Dyslipidemia • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus