756-P: A Phase 1c Evaluation of a Novel GLP-1 Analog Ecnoglutide (XW003) for Weight Loss in Adults with Overweight and Obesity

Abstract

Ecnoglutide (XW003) is a novel, long-acting GLP-1 analog being developed for the treatment of type 2 diabetes and obesity. We conducted a Phase 1c randomized, double-blind, placebo-controlled study of ecnoglutide, which enrolled 60 nondiabetic adults with BMI 24-35 kg/m2. The study was conducted in China. PK, change in mean body weight and BMI, safety, and tolerability were evaluated. Participants received 1.8 or 2.4 mg ecnoglutide or placebo as once weekly injections for 14 weeks, including dose escalation. This core treatment was followed by an open-label extension of the ecnoglutide groups, for a total duration of 26 weeks. At baseline, participants had a mean body weight of 84.61 ± 10.44 kg and BMI of 29.53 ± 1.73 kg/m2. After 14 weeks of core treatment, mean weight reduction from baseline was -8.29 ± 0.52 kg in the 1.8 mg ecnoglutide group and -7.24 ± 0.56 kg in the 2.4 mg group, compared to -0.61 ± 0.82 kg for placebo (P<0.0001 vs placebo for both doses). At Week 14, the proportion of participants achieving ≥5% weight loss from baseline was 87.5% (95% CI, 67.6 to 97.3) and 70.0% (95% CI, 45.7 to 88.1) for 1.8 and 2.4 mg ecnoglutide, respectively, and 22.2% (95% CI, 2.8 to 60.0) for placebo. Continued weight reduction was observed until the end of study at Week 26, with a mean percent change from baseline of -15.0% (95%CI, -16.8 to -13.2) and -13.2% (95% CI, -15.3 to -11.1) for 1.8 and 2.4 mg ecnoglutide, respectively. At Week 26, ≥5% weight loss was observed for 94.7% (95% CI, 74.0 to 99.9) of participants in the 1.8 mg group and 100.0% (95% CI, 75.3 to 100.0) in the 2.4 mg group. At steady state, ecnoglutide showed a mean Cmax of 310 - 468 ng/mL, Tmax of 26 - 29 h, and half-life of 139 - 162 h. Overall, ecnoglutide was safe and well tolerated. The proportion of participants reporting any AE was similar between cohorts (95.2 to 100% for ecnoglutide vs 90% for placebo). The most frequent AEs were gastrointestinal, including diarrhea and vomiting. No drug-related SAE or drug-related AEs ≥Grade 3 were reported. Disclosure G. Wang: None. W. Hu: None. H.H. Qin: Employee; Sciwind Biosciences, Sichuan Anerobic Biotech. Q. Zheng: Employee; Sciwind Biosciences. J. Ning: None. G. Mengying: None. Y. Bu: Employee; Sciwind Biosciences. C. Jones: Employee; Sciwind Biosciences. M. Fenaux: Employee; Sciwind Biosciences. Stock/Shareholder; Terns Pharmaceuticals. S. Xu: Employee; Sciwind. M.K. Junaidi: None. Funding Sciwind Biosciences