1730-P: Zenagamtide (Amycretin), a Novel Unimolecular GLP-1 and Amylin Receptor Agonist: Phase 2b Results in T2D

Introduction and Objective: Efficacy and safety of once-weekly (OW) s.c. and once-daily oral zenagamtide (amycretin) vs placebo (pbo) in adults with T2D were assessed in a phase 2b, 36-week, randomized, double-blind (within arm) study; OW s.c. data are reported. Methods: The OW s.c. part of the study consisted of 6 active treatment arms of increasing doses of zenagamtide (0.4-40 mg) and matched pbo. Adults with T2D (A1C 7.0-10.0%) on metformin ± SGLT2i were eligible. Primary endpoint: change in A1C from baseline (BL) to wk 36. Key secondary endpoints: change in body weight (BL to wk 36) and number of adverse events (AEs; BL to wk 40). Results: Zenagamtide showed a dose-dependent, statistically significantly greater change in A1C from BL to wk 36 with all doses vs pbo (Table). A higher proportion of participants achieved A1C targets (< 7%, ≤ 6.5%) with zenagamtide vs pbo. From BL to wk 36, statistically significant body weight decreases vs pbo were seen with all zenagamtide doses except 0.4 mg. No apparent weight loss plateau was seen at wk 36 with higher doses of zenagamtide. Most common AEs were gastrointestinal and the majority were mild to moderate in severity. Conclusion: In people with T2D, OW s.c. zenagamtide up to 40 mg provided significant reductions in A1C and body weight vs pbo, with a safety and tolerability profile consistent with other incretin and amylin-based therapies. These results support further investigation of zenagamtide in phase 3 trials. Disclosure P.F. Mora: Speaker's Bureau; Current; Abbott Diabetes. Advisory Panel; Current; Novo Nordisk. Speaker's Bureau; Current; Novo Nordisk, Dexcom, Inc. Consultant; Current; Medtronic. Speaker's Bureau; Current; Insulet Corporation. V. Aroda: Research Support; Current; Amgen Inc. Research Support; Ended; Applied Therapeutics. Research Support; Current; AstraZeneca. Other - Biomea; institutional consultant and research support; Current; Biomea. Research Support; Current; Boehringer Ingelheim International GmbH, Corcept Therapeutics, Eli Lilly and Company, Fractyl Health, Inc., Novo Nordisk, Pfizer Inc. Consultant; Current; Recordati S.p.A. Research Support; Current; Rhythm Pharmaceuticals, Inc. Consultant; Ended; Servier Laboratories, Mediflix, Inc., Roche Pharmaceuticals, Sanofi. Other - spouse is an employee; Current; Flagship Pioneering. Other - spouse was an employee; Ended; AditumBio, Johnson & Johnson. M. Asong: Employee; Current; Novo Nordisk A/S. Stock/Shareholder; Current; Novo Nordisk A/S. M. Bluher: Consultant; Current; Amgen Inc. Speaker's Bureau; Current; Abbott. Consultant; Current; Bayer AG, Boehringer Ingelheim International GmbH. Speaker's Bureau; Current; Daiichi Sankyo. Consultant; Current; Eli Lilly and Company, Novo Nordisk. Speaker's Bureau; Current; Merck Sharp & Dohme Corp., Sanofi, Novartis AG. L. Heftdal: Employee; Current; Novo Nordisk A/S. Stock/Shareholder; Current; Novo Nordisk A/S. A.F. Carlander: None. L.N. Vilsen: Employee; Current; Novo Nordisk. Stock/Shareholder; Current; Novo Nordisk A/S. J. Rosenstock: Advisory Panel; Ended; Amgen Inc. Research Support; Current; Amgen Inc., AstraZeneca. Advisory Panel; Ended; Biomea Fusion, Corcept Therapeutics, Eli Lilly and Company. Research Support; Ended; Eli Lilly and Company. Advisory Panel; Ended; Gan & Lee Pharmaceuticals, Hanmi Pharm. Co., Ltd., Boehringer Ingelheim International GmbH. Research Support; Ended; Boehringer Ingelheim International GmbH. Advisory Panel; Ended; Novo Nordisk. Research Support; Ended; Novo Nordisk, Pfizer Inc. Advisory Panel; Ended; Regeneron Pharmaceuticals Inc. Research Support; Ended; Regeneron Pharmaceuticals Inc. Advisory Panel; Ended; Regor. Research Support; Ended; Regor. Advisory Panel; Ended; Roche Pharmaceuticals. Advisory Panel; Current; Sanofi. Research Support; Current; Sanofi. Advisory Panel; Ended; Structure Therapeutics, Terns. Funding Supported by Novo Nordisk A/S