SAN FRANCISCO and SUZHOU, China, June 24, 2024 /PRNewswire/ — Innovent Biologics, Inc. (Innovent) (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of oncology, autoimmune, cardiovascular and metabolic, ophthalmology and other major diseases, reports the results of liver fat content from the Phase 3 study 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.
Professor Linong Ji, the leading principal investigator of the study, Peking University People’s Hospital, stated, “Metabolic dysfunction-associated fatty liver disease (MAFLD) is one of the most common chronic liver diseases in the world and the most common comorbidity in overweight and obese people in China. Metabolic dysfunction-associated fatty liver disease (MASH) and MAFLD are significant unmet clinical needs, making them hot spots for innovative drug development in the field of metabolism. In recent years, the potential of GLP-1 drugs in improving MAFLD and MASH has begun to be realized. Yet, due to the core role of glucagon in liver fat metabolism, multi-target agonists that simultaneously activate GCGR appear even more promising in the treatment of MAFLD and MASH. In the Phase 3 weight loss trial of mazdutide, we observed a significant decrease in liver fat content; the number was greater than that of GLP-1 receptor mono-agonists and other dual-target agonists as reported in other studies. This result supports that simultaneous activation of GCGR based on GLP-1R agonists may bring greater liver benefits. I look forward to further exploration of mazdutide in the treatment of MAFLD and MASH.”
In GLORY-1 trial (ClinicalTrial.gov：NCT05607680), 610 Chinese adults with BMI ≥28 kg/m2, or ≥24 kg/m2 and at least one weight-related comorbidity were randomized in a 1:1:1 ratio to receive once-weekly, subcutaneous mazdutide 4 mg, 6 mg or placebo for 48 weeks.
A total of 92 participants had an MRI scan and a liver fat content (LFC) measurement by MRI-PDFF at baseline, among whom 69 participants (25 with mazdutide 4 mg, 22 with mazdutide 6 mg and 22 with placebo) had LFC ≥5% at baseline and week 48 LFC assessment, and were included in this exploratory analysis.
Mazdutide treatment led to robust reduction in LFC and improved liver function
In 69 participants with baseline LFC ≥5% and week 48 LFC assessment, treatment with mazdutide for 48 weeks dose-dependently reduced LFC, substantially greater than placebo (mean relative change from baseline: −63.3% for mazdutide 4 mg; −73.2% for mazdutide 6 mg; 8.2% for placebo)
In participants with baseline LFC ≥10%, treatment with mazdutide 6 mg led to mean relative reduction of 80.2% in LFC at week 48.
Compared with placebo, substantially more participants with mazdutide achieved ≥30% relative reduction in LFC, ≥50% relative reduction in LFC and normalization of LFC (