maridebart cafraglutide (AMG 133) / Amgen - LARVOL DELTA

AMGEN'S PHASE 2 MARITIDE DATA TO BE PRESENTED AT THE AMERICAN DIABETES ASSOCIATION 85TH SCIENTIFIC SESSIONS (PRNewswire) - "Amgen...today announced full results from Part 1 of the Phase 2 study for MariTide (maridebart cafraglutide, formerly AMG 133) in patients living with obesity, with and without Type 2 diabetes, will be presented along with new data from the Phase 3 FOURIER study of Repatha (evolocumab) in cardiovascular disease and the VESALIUS-REAL study of real-world lipid management patterns at the 85th American Diabetes Association (ADA) Scientific Sessions taking place from June 20–23, 2025, in Chicago....The Symposium will highlight 52-week efficacy, safety and tolerability data from Part 1 of the Phase 2 study, complete data from the primary analysis of the Phase 1 pharmacokinetics low dose initiation (PK-LDI) study, and additional information on the Phase 3 MARITIME Chronic Weight Management studies."

P2 data • P3 data • Trial status • Cardiovascular • Dyslipidemia • Obesity

MariTide & Mother Nature—Rationale for the Long-acting Peptide-antibody Conjugate Molecule, Combining GLP-1 Agonism and GIP Receptor Antagonism (ADA 2025) - No abstract available

Diabetes • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Potential Impact of MariTide on the Treatment of Obesity and Type 2 Diabetes (ADA 2025) - No abstract available

Diabetes • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

MariTide Phase 2 Study—Participants with Obesity and Type 2 Diabetes (ADA 2025) - No abstract available

P2 data • Diabetes • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

MariTide Phase 2 Study—Participants with Obesity (ADA 2025) - No abstract available

P2 data • Metabolic Disorders • Obesity

Symposium - Once-Monthly MariTide for the Treatment of Obesity in People with or without Type 2 Diabetes—A 52-Week Phase 2 Study (ADA 2025) - No abstract available

P2 data • Diabetes • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

The Premise of the Paradox: Examining the Evidence That Motivated GIPR Agonist and Antagonist Drug Development Programs. (PubMed, J Clin Med) - "We focus on the physiologic role of GIP in humans, human genetics evidence, rodent genetic models, and preclinical rodent and non-human primate pharmacology studies. Furthermore, we highlight where early preclinical findings translated into relevant clinical efficacy in the development of tirzepatide and maridebart cafraglutide (MariTide)."

Journal • Review • Genetic Disorders

A comparison of the metabolic effects of a long-acting GIPR agonist versus a GIPR antagonist (ENDO 2025) - "Moreover, both tirzepatide (a GLP-1R/GIPR dual agonist) and AMG133 (a GLP-1R agonist/ GIPR antagonist) appear to outperform GLP-1R mono-agonists with regards to weight loss in clinical trials. Moreover, the observation that GIP108 was unable to prevent GLP-1RA induced emesis, an effect induced by other GIPR agonists, highlights the heterogeneity in CNS responses induced by different GIPR agonists. A comparison of the metabolic effectiveness of both approaches in humans is an important area of future study."

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

MARITIME-3-J: Efficacy and Safety of Maridebart Cafraglutide in Adult Participants in Japan Who Have Obesity Disease (clinicaltrials.gov) - P3 | N=272 | Not yet recruiting | Sponsor: Amgen

New P3 trial • Genetic Disorders • Obesity

A Study to Evaluate AMG 133 Administered Subcutaneously in Participants With Overweight or Obesity (clinicaltrials.gov) - P1 | N=120 | Completed | Sponsor: Amgen

New P1 trial • Genetic Disorders • Obesity

A Study of Maridebart Cafraglutide in Adult Participants With Type 2 Diabetes Mellitus (T2DM) (clinicaltrials.gov) - P2 | N=399 | Active, not recruiting | Sponsor: Amgen | Recruiting ➔ Active, not recruiting

Enrollment closed • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

MARITIME-2: Efficacy and Safety of Maridebart Cafraglutide in Adult Participants With Type 2 Diabetes Mellitus Who Have Obesity or Are Overweight (clinicaltrials.gov) - P3 | N=999 | Recruiting | Sponsor: Amgen | Not yet recruiting ➔ Recruiting

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

MARITIME-1: Evaluation of Maridebart Cafraglutide in Adult Participants Without Type 2 Diabetes Mellitus Who Have Obesity or Are Overweight (clinicaltrials.gov) - P3 | N=3501 | Recruiting | Sponsor: Amgen | Not yet recruiting ➔ Recruiting

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

Multifunctional incretin peptides in therapies for type 2 diabetes, obesity and associated co-morbidities. (PubMed, Peptides) - "Recent studies with peptide-based incretin herapies have focussed mainly on the glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide and the dual agonist tirzepatide that engages receptors for GLP-1 and glucose-dependent insulinotropic polypeptide (GIP)...New incretin-based peptide therapies in development include a long-acting glucagon receptor agonist (LY3324954), dual GLP-1/glucagon receptor agonists (survodutide, pemvidutide, mazdutide, G49), triple GLP-1/GIP/glucagon receptor agonists (retatrutide, efocipegtrutide), a combination of semaglutide with the amylin analogue cagrilintide (CagriSema), a unimolecular GLP-1/amylin receptor dual agonist (amycretin), and a GIP receptor antibody with GLP-1 receptor agonism (MariTide). The creation of multi-targeting incretin-based synthetic peptides provides opportunities for improved management of type 2 diabetes and obesity as well as new therapeutic approaches to an expanding list of associated co-morbidities. The..."

Journal • Cardiovascular • Diabetes • Genetic Disorders • Hepatology • Inflammation • Metabolic Disorders • Nephrology • Obesity • Obstructive Sleep Apnea • Orthopedics • Renal Disease • Respiratory Diseases • Sleep Apnea • Sleep Disorder • Type 2 Diabetes Mellitus

MARITIME-1: Evaluation of Maridebart Cafraglutide in Adult Participants Without Type 2 Diabetes Mellitus Who Have Obesity or Are Overweight (clinicaltrials.gov) - P3 | N=3501 | Not yet recruiting | Sponsor: Amgen

New P3 trial • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

MARITIME-2: Efficacy and Safety of Maridebart Cafraglutide in Adult Participants With Type 2 Diabetes Mellitus Who Have Obesity or Are Overweight (clinicaltrials.gov) - P3 | N=999 | Not yet recruiting | Sponsor: Amgen

New P3 trial • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

AMGEN REPORTS FOURTH QUARTER AND FULL YEAR 2024 FINANCIAL RESULTS (PRNewswire) - "MariTide (maridebart cafraglutide, AMG 133): Part 2 of the Phase 2 chronic weight management study is ongoing in adults who are living with overweight or obesity, with or without Type 2 diabetes mellitus. Data readout is anticipated in H2 2025. A Phase 2 study investigating MariTide for the treatment of Type 2 diabetes mellitus is enrolling adults living with and without obesity. Data readout is anticipated in H2 2025. Planning for MARITIME, a broad Phase 3 program across multiple indications remains on track with the first studies expected to begin in H1 2025....AMG 513: A Phase 1 study of AMG 513 in people living with obesity was placed on clinical hold by the U.S. Food and Drug Administration (FDA)."

New P3 trial • P2 data • Trial suspension • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Glucose-dependent insulinotropic polypeptide receptor signaling alleviates gut inflammation in mice. (PubMed, JCI Insight) - "The clinical development of GIP receptor (GIPR)-GLP-1 receptor (GLP-1R) multi-agonists exemplified by tirzepatide and emerging GIPR antagonist-GLP-1R agonist therapeutics such as maritide is increasing interest in the extra-pancreatic actions of incretin therapies...Here, using gain and loss of function studies, we show that GIP alleviates 5-fluorouracil (5FU)-induced gut inflammation, whereas genetic deletion of Gipr exacerbates the proinflammatory response to 5FU in the murine small bowel (SB)...Within the gut, Gipr was localized to non-immune cells, specifically stromal CD146+ cells. Hence, the extra-pancreatic actions of GIPR signaling extend to the attenuation of gut inflammation, findings with potential translational relevance for clinical strategies modulating GIPR action in people with type 2 diabetes or obesity."

Journal • Preclinical • Diabetes • Endocrine Disorders • Genetic Disorders • Inflammation • Inflammatory Bowel Disease • Metabolic Disorders • Obesity • Transplantation • Type 2 Diabetes Mellitus • MCAM

A Study of Maridebart Cafraglutide in Adult Participants With Type 2 Diabetes Mellitus (T2DM) (clinicaltrials.gov) - P2 | N=350 | Recruiting | Sponsor: Amgen | Not yet recruiting ➔ Recruiting

Enrollment open • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

AMGEN ANNOUNCES ROBUST WEIGHT LOSS WITH MARITIDE IN PEOPLE LIVING WITH OBESITY OR OVERWEIGHT AT 52 WEEKS IN A PHASE 2 STUDY (Amgen Press Release) - P2 | N=592 | NCT05669599 | Sponsor: Amgen | "Amgen...today announced positive data at 52 weeks in a double-blind, dose-ranging Phase 2 study with MariTide....In people living with obesity or overweight without Type 2 diabetes, MariTide demonstrated up to ~20% average weight loss at week 52 without a weight loss plateau, indicating the potential for further weight loss beyond 52 weeks. The study also showed people living with obesity or overweight and Type 2 diabetes, who typically lose less weight on GLP-1 therapies, achieved up to ~17% average weight loss, also without a weight loss plateau, and lowered their average hemoglobin A1C (HbA1c) by up to 2.2 percentage points at week 52. In summary, in both study populations, a weight loss plateau was not observed, again indicating the potential for further weight loss beyond 52 weeks. MariTide also demonstrated robust and clinically meaningful improvements in cardiometabolic parameters..."

P2 data • Metabolic Disorders • Obesity

A Study of Maridebart Cafraglutide in Adult Participants With Type 2 Diabetes Mellitus (T2DM) (clinicaltrials.gov) - P2 | N=350 | Not yet recruiting | Sponsor: Amgen

New P2 trial • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

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

Trial completion • Genetic Disorders • Obesity

Characterization of genetic variants of GIPR reveals a contribution of β-arrestin to metabolic phenotypes. (PubMed, Nat Metab) - "Yet both activation and inhibition of the glucose-dependent insulinotropic polypeptide (GIP) receptor (GIPR) in combination with glucagon-like peptide-1 (GLP-1) receptor (GLP-1R) activation have resulted in similar clinical outcomes, as demonstrated by the GIPR-GLP-1R co-agonist tirzepatide2 and AMG-133 (ref. Endosomal Gs-mediated signalling of the variants shows a β-arrestin dependency and genetic ablation of β-arrestin 2 impairs cyclic adenosine monophosphate production and decreases GIP efficacy on glucose control in male mice. This study highlights a crucial impact of β-arrestins in regulating GIPR signalling and overall preservation of biological activity that may facilitate new developments in therapeutic targeting of the GIPR system."

Journal • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus • ARRB1

Efficacy and Safety of GLP-1 Medicines for Type 2 Diabetes and Obesity. (PubMed, Diabetes Care) - "The success of GLP-1-based medicines has spurred the development of new molecular entities and combinations with unique pharmacokinetic and pharmacodynamic profiles, exemplified by tirzepatide, a GIP-GLP-1 receptor coagonist. Simultaneously, investigational molecules such as maritide block the GIP and activate the GLP-1 receptor, whereas retatrutide and survodutide enable simultaneous activation of the glucagon and GLP-1 receptors. Here I highlight evidence establishing the efficacy of GLP-1-based medicines, while discussing data that inform safety, focusing on muscle strength, bone density and fractures, exercise capacity, gastrointestinal motility, retained gastric contents and anesthesia, pancreatic and biliary tract disorders, and the risk of cancer. Rapid progress in development of highly efficacious GLP-1 medicines, and anticipated differentiation of newer agents in subsets of metabolic disorders, will provide greater opportunities for use of personalized medicine..."

Journal • Review • Alzheimer's Disease • Anesthesia • Cardiovascular • CNS Disorders • Diabetes • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Hepatology • Metabolic Disorders • Movement Disorders • Musculoskeletal Diseases • Obesity • Oncology • Parkinson's Disease • Peripheral Arterial Disease • Type 2 Diabetes Mellitus

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

Enrollment closed • Genetic Disorders • Obesity