Innovent Reports 80.2% Liver Fat Reduction in Phase 3 GLORY-1 Study

Innovent Biologics, Inc. (Innovent), a globally recognized biopharmaceutical company, has announced the results of its Phase 3 study on mazdutide for reducing liver fat content in overweight or obese Chinese adults. This study, known as GLORY-1, was presented at the ADA scientific sessions in 2024.

Mazdutide, identified by Innovent's R&D code IBI362, is a dual agonist targeting the GLP-1 receptor (GLP-1R) and the glucagon receptor (GCGR). By activating GLP-1R, mazdutide reduces appetite and delays gastric emptying, which contributes to weight loss. Simultaneously, the activation of GCGR boosts energy expenditure, enhances fatty acid oxidation, promotes lipolysis, and decreases liver fat.

Professor Linong Ji from Peking University People's Hospital, the lead investigator of the study, highlighted the significance of metabolic dysfunction-associated fatty liver disease (MAFLD) and metabolic dysfunction-associated steatohepatitis (MASH). These conditions are prevalent comorbidities in overweight and obese individuals in China and represent significant clinical needs. Ji noted the emerging potential of GLP-1 drugs in treating these conditions. However, due to glucagon's pivotal role in liver fat metabolism, dual-target agonists like mazdutide show even greater promise.

The GLORY-1 trial involved 610 Chinese adults with a Body Mass Index (BMI) of ≥28 kg/m², or ≥24 kg/m² with at least one weight-related comorbidity. Participants were randomly assigned to receive either 4 mg or 6 mg of mazdutide, or a placebo, administered weekly for 48 weeks. Of these participants, 92 underwent MRI scans to measure liver fat content (LFC) using MRI-PDFF at the start and end of the study. This exploratory analysis focused on 69 participants who had an LFC of ≥5% at baseline and completed the week 48 assessment.

Results showed that mazdutide significantly reduced LFC in a dose-dependent manner compared to the placebo. The mean relative change in LFC from baseline was -63.3% for the 4 mg dose and -73.2% for the 6 mg dose, while the placebo group saw an 8.2% increase. In participants with a baseline LFC of ≥10%, the 6 mg dose resulted in an 80.2% reduction in LFC by week 48.

Furthermore, a higher percentage of participants in the mazdutide groups achieved substantial LFC reductions. Specifically, 95.5% of those on the 6 mg dose achieved at least a 30% reduction, and 77.3% reached normalization of LFC (<5%) by the end of the study. Mazdutide also improved other health indicators, including body weight, waist circumference, blood pressure, transaminase levels, and lipid profiles.

Dr. Lei Qian, Vice President of Clinical Development at Innovent, emphasized the importance of mazdutide's dual action on GLP-1R and GCGR in improving liver fat metabolism. The promising results from the GLORY-1 study support further investigation into mazdutide's clinical value for treating MAFLD and MASH.

Obesity, a chronic disease with multifactorial causes, is a major risk factor for type 2 diabetes, cardiovascular diseases, fatty liver, and various cancers. With lifestyle changes and economic development, China now has one of the largest obese populations globally. Traditional pharmacological treatments in China have shown limited efficacy and safety, highlighting the need for more effective and safe interventions for obesity.

Mazdutide, developed under an exclusive license agreement with Eli Lilly for the Chinese market, is an OXM analogue with dual GLP-1R and GCGR agonist properties. It has demonstrated significant weight loss, blood glucose reduction, and improvements in multiple cardio-metabolic indicators in clinical studies. Currently, five Phase 3 studies are evaluating mazdutide in various populations, with two having already met their primary and secondary endpoints.

Founded in 2011, Innovent Biologics aims to provide high-quality, affordable biopharmaceuticals worldwide. The company focuses on developing treatments for cancer, cardiovascular, metabolic, autoimmune, and eye diseases, with several products already in the market and numerous others in various stages of clinical development.