79-LB: An Open-Label, Active-Controlled Phase 2 Evaluation of Novel GLP-1 Analog Ecnoglutide in Adults with Obesity

Abstract

Ecnoglutide (XW003) is a novel, long-acting GLP-1 analog being developed for the treatment of type 2 diabetes mellitus (T2DM) and obesity. We conducted a multi-center, open-label, active-controlled Phase 2b study in adults with a body mass index (BMI) ≥30 to ≤40 kg/m2. The trial was conducted at nine sites in Australia and New Zealand, with 206 participants enrolled. Participants were randomized to receive target doses of ecnoglutide at 1.2, 1.8, or 2.4 mg as once weekly SC injections or liraglutide (Saxenda®) at 3.0 mg as once daily injections for 26 weeks. Doses were increased by titration for up to 14 weeks before reaching the target dose. Safety and tolerability were assessed, along with efficacy parameters including change in body weight. At baseline, participants had a mean body weight of 100.67 ± 13.54 kg and BMI of 35.29 ± 2.76 kg/m2. After 26 weeks of dosing, participants receiving 1.2, 1.8, or 2.4 mg ecnoglutide weekly achieved a least square mean (LSM) body weight reduction from baseline of -11.5%, -11.2%, and -14.7%, respectively, compared to -8.8% for those receiving 3.0 mg liraglutide daily injections. Participants receiving 2.4 mg ecnoglutide showed significantly more pronounced body weight reduction compared to liraglutide (LSM difference -5.9, 95% confidence interval -10.4, -1.5; p<0.001). Overall, treatment with ecnoglutide was safe and well tolerated. Treatment emergent AEs were reported in 93.5% of participants in the ecnoglutide groups and 98.0% in the liraglutide group. Gastrointestinal disorders were reported in 81.9% of ecnoglutide-treated participants and 80.4% of those receiving liraglutide, most of which were mild to moderate and most occurred during the dose escalation period. Two SAEs related to the study drug were reported. Both were cases of acute cholecystitis, one in a participant receiving 1.2 mg ecnoglutide and one in the liraglutide group. Disclosure Z. Zhu: Employee; Sciwind Biosciences. M. K. Junaidi: None. Y. Li: Employee; Sciwind Biosciences. Q. Zheng: Employee; Sciwind Biosciences. E. Adegbite: Employee; Sciwind Biosciences. S. Ross: None. L. Telusca: None. C. L. Jones: Employee; Sciwind Biosciences. M. Fenaux: Employee; Sciwind Biosciences, Stock/Shareholder; Terns Pharmaceuticals. S. Xu: Employee; Sciwind. Funding Sciwind Biosciences Co., Ltd.