ODP014 Safety and Efficacy of IBI362 (LY3305677) 9 mg and 10 mg in Chinese Adults with Overweight or Obesity

Abstract Background IBI362, a novel once-weekly glucagon-like peptide-1 (GLP-1) and glucagon receptor dual agonist, achieved 12-week weight loss up to 6.4% at doses up to 6 mg in Chinese participants with overweight or obesity. We further explored the safety and efficacy of IBI362 dosed up to 9 mg and 10 mg. Methods Two high-dose cohorts from a randomized, placebo-controlled, multiple ascending dose study (NCT04440345) enrolled adults with overweight (body mass index [BMI] ≥24 kg/m 2) accompanied by hyperphagia and/or at least one comorbidity or obesity (BMI≥28 kg/m 2) from five study centers in China. Eligible participants were randomized 2: 1 within each cohort to receive once-weekly subcutaneous IBI362 or placebo. The cohorts and dose-escalation regimens were: 9 mg cohort (3 mg weeks 1-4; 6 mg weeks 5-8; 9 mg weeks 9-12) and 10 mg cohort (2.5 mg weeks 1-4; 5 mg weeks 5-8; 7.5 mg weeks 9-12; 10 mg weeks 13-16). The primary endpoints were safety and tolerability of IBI362. The secondary endpoints included changes from baseline in body weight, waist circumference and BMI. Results A total of 24 participants (mean age 37.9 years, body weight 81. 0 kg, BMI 30.5 kg/m 2) were enrolled, with eight randomly assigned to IBI362 and four to placebo in each cohort. One participant receiving IBI362 and two receiving placebo in the 10 mg cohort withdrew consent and quitted the study. The other 21 participants (87.5%) completed the treatment and the study. No serious adverse event (AE) was reported and all AEs were mild or moderate in severity. The most commonly-reported AEs included diarrhea, nausea, vomiting and decreased appetite (each reported in six participants [37.5%] receiving IBI362). Mean percent changes from baseline to week 12 in body weight were−11.7% for participants receiving IBI362 in the 9 mg cohort and−1.8% for participants receiving placebo (estimated treatment difference [ETD]: −9.8%; 95% confidence interval (CI): −14.4,−5.3; P = 0. 0002). Mean percent changes from baseline to week 16 in body weight were−9.5% for participants receiving IBI362 in the 10 mg cohort and−3.3% for participants receiving placebo (ETD: −6.2%; 95% CI: −11.5,−0.9; P = 0. 0243). Four participants (50%) receiving IBI362 in each cohort achieved≥10% weight loss and two (25%) receiving IBI362 in each cohort achieved≥15% weight loss during the study, while no participant receiving placebo achieved≥5% weight loss. In addition, waist circumference and BMI were markedly decreased in participants receiving IBI362. Conclusion IBI362 dosed up to 9 mg and 10 mg was both well tolerated and showed a favorable safety profile. IBI362 dosed with the 3-6-9 mg escalation regimen demonstrated extraordinary efficacy on 12-week weight loss, suggesting that IBI362 would be a promising weight loss drug as the next generation GLP-1-based dual agonist. Presentation: No date and time listed