Mazdutide 9 mg achieves up to 20.1% weight loss as GLORY-2 Study meets primary and all key secondary endpoints

Outcomes from the Phase 3 clinical trial of mazdutide, a first-in-class dual glucagon (GCG)/glucagon-like peptide-1 (GLP-1) receptor agonist, in Chinese adults with obesity (GLORY-2) has met the primary endpoints and all key secondary endpoints. Innovent Biologics plans to submit the new drug application (NDA) of mazdutide 9 mg for weight management to the Center for Drug Evaluation (CDE) of China's National Medical Products Administration (NMPA) in the near term.

GLORY-2 is a Phase 3 clinical study to evaluate the efficacy and safety of mazdutide 9 mg combined with lifestyle intervention versus placebo in Chinese adults with obesity (BMI ≥30 kg/m²). The study enrolled 462 participants (including 16% with type 2 diabetes), randomized in a 2:1 ratio to receive mazdutide 9 mg group or placebo in the 60-week double-blind treatment period (mean baseline weight: 94.0 kg; mean BMI: 34.3 kg/m²).

During the treatment period, participants in the mazdutide group exhibited continuous weight loss, with no plateau observed in Week 60. At Week 60, the mazdutide 9 mg group achieved a mean weight reduction of 18.55%, compared to 3.02% in the placebo group. 44.0% of participants in the mazdutide 9 mg group achieved a weight reduction of 20% or more, versus 2.6% in the placebo group (p<0.0001 for all comparisons). The key secondary endpoints demonstrated that among participants without type 2 diabetes, the mazdutide 9 mg group showed a mean weight reduction of 20.08% at Week 60 (placebo: 2.81%), with 48.7% of participants achieving a weight reduction of 20% or more (placebo: 3.1%; p<0.0001).

Furthermore, all key secondary endpoints of the study were met, including other body weight endpoints, waist circumference, systolic blood pressure, triglycerides, non-HDL cholesterol, LDL cholesterol, and serum uric acid levels. Mazdutide 9 mg demonstrated superiority to placebo in all the above weight-loss and cardiometabolic endpoints.

This study also evaluated liver fat content using MRI-PDFF in a subset of participants. Among participants (without type 2 diabetes) with baseline liver fat content ≥10%, the mean percent change in liver fat content from baseline to week 60 was -71.9% in the mazdutide 9 mg group compared with 5.1% in the placebo group.

Mazdutide 9 mg demonstrated favourable tolerability and safety profiles, with no new safety signals identified. The majority of gastrointestinal adverse events were mild to moderate in severity and transient in nature. The proportion of participants who discontinued treatment prematurely due to adverse events was 2.9% in the mazdutide 9 mg group and 0% in the placebo group.

Mazdutide has received NMPA approval for two indications - as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adult patients with an initial Body Mass Index (BMI) ≥ 28 kg/m² (obesity); or BMI ≥ 24 kg/m² (overweight) in the presence of at least one weight-related comorbid condition (e.g., hyperglycaemia, hypertension, dyslipidaemia, fatty liver, or obstructive sleep apnoea syndrome). The second indication is for glycaemic control in adults with type 2 diabetes.

Innovent entered into an exclusive license agreement with Eli Lilly and Company (Lilly) for the development and potential commercialization of mazdutide, a dual GCG/GLP-1 receptor agonist, in China.