maridebart cafraglutide (AMG 133) / Amgen - LARVOL DELTA

A Study to Evaluate AMG 133 in Chinese Participants With Obesity or Overweight (clinicaltrials.gov) - P1 | N=20 | Not yet recruiting | Sponsor: Amgen

New P1 trial • Genetic Disorders • Obesity

Phase I results for AMG 133. (PubMed, Nat Rev Endocrinol) - No abstract available

Journal • P1 data

A GIPR antagonist conjugated to GLP-1 analogues promotes weight loss with improved metabolic parameters in preclinical and phase 1 settings. (PubMed, Nat Metab) - P1 | "In the multiple ascending dose cohorts, weight loss was maintained for up to 150 days after the last dose. These findings support continued clinical evaluation of AMG 133."

Clinical • Journal • P1 data • Preclinical • Genetic Disorders • Obesity

Dose-ranging Study to Evaluate the Efficacy, Safety, and Tolerability of AMG 133 in Adult Participants With Overweight or Obesity, With or Without Type 2 Diabetes Mellitus (clinicaltrials.gov) - P2 | N=592 | Active, not recruiting | Sponsor: Amgen | Recruiting ➔ Active, not recruiting

Enrollment closed • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus • CRP

Dose-ranging Study to Evaluate the Efficacy, Safety, and Tolerability of AMG 133 in Adult Participants With Overweight or Obesity, With or Without Type 2 Diabetes Mellitus (clinicaltrials.gov) - P2 | N=570 | Recruiting | Sponsor: Amgen | Trial completion date: Dec 2024 ➔ Dec 2025

Trial completion date • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus • CRP

AMGEN REPORTS SECOND QUARTER FINANCIAL RESULTS (PRNewswire) - "A Phase 2 study of maridebart cafraglutide, a multispecific molecule that inhibits the gastric inhibitory polypeptide receptor (GIPR) and activates the glucagon like peptide 1 (GLP-1) receptor, in overweight or obese adults with or without type 2 diabetes mellitus continues to enroll patients."

Enrollment status • Metabolic Disorders • Obesity

A Novel GIPR Antagonist Antibody and GLP-1 Peptide Conjugate (AMG 133) for Treatment of Obesity (PEGS 2023) - "In human Phase 1 trial AMG 133 demonstrated weight loss and tolerability. The design, conjugation process, and preclinical activity will be discussed."

Genetic Disorders • Obesity

Dose-ranging Study to Evaluate the Efficacy, Safety, and Tolerability of AMG 133 in Adult Participants With Overweight or Obesity, With or Without Type 2 Diabetes Mellitus (clinicaltrials.gov) - P2 | N=570 | Recruiting | Sponsor: Amgen | Not yet recruiting ➔ Recruiting

Enrollment open • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus • CRP

An update on peptide-based therapies for type 2 diabetes and obesity. (PubMed, Peptides) - "Of note is the GLP-1R agonist semaglutide, available in oral and injectable formulations and in clinical trials combined with the long-acting amylin analogue, cagrilintide. Particularly high efficacy in both glucose- and weight lowering capacities has also been observed with the GLP-1R/GIP-R unimolecular dual agonist, tirzepatide...Other pharmacological approaches to chronic weight management include the human monoclonal antibody, bimagrumab which blocks activin type II receptors and is associated with growth of skeletal muscle, an antibody blocking activation of GIPR to which are conjugated GLP-1R peptide agonists (AMG-133), and the melanocortin-4 receptor agonist, setmelanotide for use in certain inherited obesity conditions. The high global demand for the GLP-1R agonists liraglutide and semaglutide as anti-obesity agents has led to shortage so that their use in T2D therapy is currently being prioritized."

Journal • Review • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Dose-ranging Study to Evaluate the Efficacy, Safety, and Tolerability of AMG 133 in Adult Participants With Overweight or Obesity, With or Without Type 2 Diabetes Mellitus (clinicaltrials.gov) - P2 | N=570 | Not yet recruiting | Sponsor: Amgen

New P2 trial • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus • CRP

Beyond the pancreas: contrasting cardiometabolic actions of GIP and GLP1. (PubMed, Nat Rev Endocrinol) - "We interpret the clinical and mechanistic data obtained for different agents that enable weight loss and glucose control for the treatment of obesity and type 2 diabetes mellitus, respectively, by activating or blocking GIPR signalling, including the GIPR-GLP1R co-agonist tirzepatide, as well as the GIPR antagonist-GLP1R agonist AMG-133. Collectively, we update translational concepts of GIP and GLP1 action, while highlighting gaps, areas of uncertainty and controversies meriting ongoing investigation."

Journal • Review • Atherosclerosis • Cardiovascular • Diabetes • Dyslipidemia • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Single and Multiple Ascending Dose Study of AMG 133 in Participants With Obesity (clinicaltrials.gov) - P1 | N=110 | Completed | Sponsor: Amgen | Active, not recruiting ➔ Completed

Trial completion • Genetic Disorders • Obesity

"Still difficult to understand how GIPR agonism (tirzepatide) and antagonism (AMG-133) can both bring additional benefits to GLP-1R agonism…" (@bernardkhoo)

"$AMGN great stuff. AMG133, Olpasarin, Evolocumab. #AHA22." (@princetongb)

Single and Multiple Ascending Dose Study of AMG 133 in Participants With Obesity (clinicaltrials.gov) - P1 | N=110 | Active, not recruiting | Sponsor: Amgen | Recruiting ➔ Active, not recruiting

Enrollment closed • Genetic Disorders • Obesity

Single and Multiple Ascending Dose Study of AMG 133 in Participants With Obesity (clinicaltrials.gov) - P1 | N=112 | Recruiting | Sponsor: Amgen | Active, not recruiting ➔ Recruiting | Trial completion date: May 2022 ➔ Nov 2022 | Trial primary completion date: May 2022 ➔ Nov 2022

Enrollment open • Trial completion date • Trial primary completion date • Genetic Disorders • Obesity

Study of AMG 133 Administered Subcutaneously in Healthy Japanese and Caucasian Participants (clinicaltrials.gov) - P1 | N=34 | Completed | Sponsor: Amgen | Active, not recruiting ➔ Completed

Trial completion

Study of AMG 133 Administered Subcutaneously in Healthy Japanese and Caucasian Participants (clinicaltrials.gov) - P1; N=34; Active, not recruiting; Sponsor: Amgen; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed

Single and Multiple Ascending Dose Study of AMG 133 in Participants With Obesity (clinicaltrials.gov) - P1; N=100; Active, not recruiting; Sponsor: Amgen; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • Genetic Disorders • Obesity

Study of AMG 133 Administered Subcutaneously in Healthy Japanese and Caucasian Participants (clinicaltrials.gov) - P1; N=35; Recruiting; Sponsor: Amgen; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open

Study of AMG 133 Administered Subcutaneously in Healthy Japanese and Caucasian Participants (clinicaltrials.gov) - P1; N=35; Not yet recruiting; Sponsor: Amgen

New P1 trial

Emerging glucagon-like peptide 1 receptor agonists for the treatment of obesity. (PubMed, Expert Opin Emerg Drugs) - "There is a strong interest in developing obesity treatments based on glucagon-like peptide-1 (GLP-1) agonism, which have proved to limit morbidity and mortality in type 2 diabetes.Areas covered: This review provides an overview of current compounds containing GLP-1 receptor agonism in clinical development for obesity, with mono-activity at the GLP-1 receptor (PF-0688296, glutazumab, semaglutide) or engaging one or more other endogenous hormonal systems involved in energy balance and metabolism, including glucagon, oxyntomodulin, glucose-dependent inhibitory peptide and amylin (CT-868, CT-388, AMG 133, tirzepatide, NNC9204-1177, JNJ-54728518, SAR425899, pegapamodutide, MK8521, cotadutide, efinopegdutide, BI-456906, cagrilintide + semaglutide 2,4 mg, HM15211, NNC9204-1706).Expert opinion: Many novel compounds employing GLP-1 receptor agonism are in clinical development. Semaglutide is farthest in clinical development and will presumably become a benchmark for this class of..."

Journal • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Single and Multiple Ascending Dose Study of AMG 133 in Participants With Obesity (clinicaltrials.gov) - P1; N=92; Recruiting; Sponsor: Amgen; N=48 ➔ 92

Clinical • Enrollment change • Genetic Disorders • Obesity

Single Ascending Dose Study of AMG 133 in Subjects With Obesity (clinicaltrials.gov) - P1; N=48; Recruiting; Sponsor: Amgen; Trial primary completion date: Oct 2021 ➔ Apr 2022

Clinical • Trial primary completion date • Genetic Disorders • Obesity

Single Ascending Dose Study of AMG 133 in Subjects With Obesity (clinicaltrials.gov) - P1; N=48; Recruiting; Sponsor: Amgen; Trial completion date: Oct 2021 ➔ Feb 2022

Clinical • Trial completion date • Genetic Disorders • Obesity