Innovent Biologics, Inc. presents the key results of the first Phase 3 clinical trial of mazdutide in Chinese adults with overweight or obesity (GLORY-1) at the ADA Scientific Sessions 2024. Mazdutide (Innovent R&D code: IBI362) is a glucagon-like peptide-1 receptor (GLP-1R) and glucagon receptor (GCGR) dual agonist. By activating GLP-1R, it reduces appetite and delays gastric emptying, thereby achieving weight loss.

At the same time, through activation of GCGR, it increases energy expenditure, enhances fatty acid oxidation and lipolysis, and reduces liver fat. The results of the GLORY-1 study demonstrated that mazdutide not only induced robust weight loss in adults with obesity or overweight, but also reduced liver fat content and multiple cardiometabolic risk factors. Its first new drug application (NDA) for chronic weight management is under review by the CDE of the National Medical Products Administration (NMPA).

Mazdutide, once approved, is expected to provide a safe and convenient medication for adults with obesity or overweight to effectively reduce body weight while providing cardiovascular and metabolic benefits. Full results and analysis of GLORY-1 will be published at peer-reviewed academic journals. At present, over 1,500 subjects have received doses of mazdutide in 17 clinical trials, providing solid clinical evidence for weight management and diabetes treatment in China.

GLORY-1 (NCT05607680) is a multi-center, randomized, double-blind, placebo-controlled Phase 3 clinical trial to evaluate the efficacy and safety of mazdutide in Chinese adults with overweight or obesity. A total of 610 participants were randomized to receive mazdutide 4 mg, 6 mg or placebo in the 48-week double-blind treatment period. At week 32 and week 48, the weight loss efficacy of mazdutide 4mg and 6mg were superior to placebo in the mean percentage change in body weight from baseline, and percentage of participants achieved body weight reduction =5%, =10% and =15% (P<0.001).

At week 48, the treatment difference for the mean percentage weight change between mazdutide 6 mg and placebo was -14.31% for the treatment-policy estimand and -14.37% for the efficacy estimand. For the efficacy estimand (P<0.001 for comparisons), At week 48, the change from baseline to week 48 in waist circumference was -9.48 cm with mazdutide 4 mg, -10.96 cm with mazdutide 6 mg and -1.48 cm with placebo; At week 48, pooled mazdutide group (4mg and 6mg) significantly reduced multiple indicators of cardiometabolic risk factors compared with placebo, including systolic blood pressure (-9.21 mmHg vs. -2.46 mmHg), triglycerides (-0.68 mmol/L vs.

-0.16 mmol/L), total cholesterol (-0.32 mmol/L vs. 0.13 mmol/L), low-density lipoprotein cholesterol (-0.22 mmol/L vs. 0.09 mmol/L), serum uric acid (-44.79 µmol/L vs.

5.96 µmol/L) and ALT (-14.50 U/L vs.-4.50 U/L); Mazdutide showed marked reductions of liver fat content: As shown in an exploratory analysis of GLORY-1(1857-LB), in participants with baseline MRI-PDFF =10%, the liver fat content in mazdutide 6mg group was reduced by 80.2% on average, compared with 5.3% with placebo. The overall tolerability and safety profile of mazdutide was favorable with no new safety signals observed: Mazdutide was well tolerated. 1.5%, 0.5% and 1.0% of participants in the mazdutide 4 mg group, mazdutide 6 mg group and placebo group discontinued the study drug prematurely due to AEs.

The safety profile was consistent with that observed in previous studies of mazdutide, with no new safety signals observed. The most frequently reported adverse events were gastrointestinal (nausea, diarrhea and vomiting), mostly mild or moderate in severity and occurring during dose escalation. The incidence of serious adverse events was low and comparable to placebo.

Mean changes from baseline in heart rate were no more than 5 beats/min throughout the 48-week treatment period for both the mazdutide 4mg and 6mg groups. The mean change from baseline to week 48 in heart rate were 1.6 beats/min in both mazdutide 4 mg and 6 mg groups. No safety signal of increased cardiovascular risk was observed during treatment.