Mazdutide vs. Semaglutide Phase 3 Study Starts Dosing in Chinese Adults with Obesity and Fatty Liver Disease

Innovent Biologics, Inc. has recently made strides in the field of biopharmaceuticals by initiating the GLORY-3 Phase 3 clinical trial, marking a significant development in the treatment of metabolic dysfunction-associated fatty liver disease (MAFLD) and obesity. This groundbreaking study has successfully dosed its first participant and aims to evaluate the efficacy and safety of mazdutide—a novel dual glucagon (GCG) and glucagon-like peptide 1 receptor (GLP-1) agonist—against semaglutide in overweight or obese Chinese adults suffering from MAFLD.

The GLORY-3 study is comprehensive in its approach, enrolling approximately 470 participants with a body mass index (BMI) of 27 kg/m² or higher, coupled with MAFLD. Participants are randomly assigned to receive either mazdutide at a dose of 9 mg or semaglutide at a dose of 2.4 mg. The study's primary focus is the percentage change in liver fat content (LFC), measured using magnetic resonance proton density fat fraction (MRI-PDFF), and the percentage change in body weight at the 48-week mark.

Historical data from a preceding Phase 2 study highlighted the potential of mazdutide in weight management and liver health. In that study, participants with obesity (BMI ≥ 30 kg/m²) who were administered mazdutide showed a considerable placebo-adjusted mean percent reduction in body weight by 18.6% over 48 weeks. Additionally, significant portions of the participants achieved substantial weight loss benchmarks—15% or more and 20% or more from baseline. Also noteworthy was the reduction in liver fat content, with a dramatic 73.3% decrease among those with a baseline LFC of 5% or greater, which persisted throughout the extended treatment period.

Professor Lixin Guo, serving as the Principal Investigator, emphasized the growing prevalence of MAFLD as the most widespread chronic liver disease globally, especially in China, where it has surpassed viral hepatitis. With obesity being a major risk factor, Chinese guidelines now advocate for GLP-1 agents, like semaglutide, in treating these conditions. Mazdutide's dual receptor agonist mechanism offers benefits beyond those of single agonist drugs, due in part to its additional GCG activity. The GLORY-3 trial, therefore, stands as a pioneering effort to contrast these treatments head-to-head, with the ultimate goal of providing enhanced therapeutic options for the Chinese population battling obesity and MAFLD.

Dr. Lei Qian, Innovent's Senior Vice President of Clinical Development, expressed optimism regarding mazdutide’s ability to deliver comprehensive metabolic advantages. The drug’s dual action is believed to stimulate lipolysis and fatty acid oxidation more effectively than GLP-1 receptor agonists alone. Early results from the Phase 2 study support expectations of mazdutide continuing to show strong clinical efficacy in terms of weight reduction and liver metabolism throughout the GLORY-3 trial, potentially offering improved treatments for patients in China.

Obesity remains a pressing public health concern in China, with predictions pointing to a rising obesity rate. It is a significant contributor to numerous health complications, thus necessitating effective long-term management strategies. In 2019, obesity accounted for a notable percentage of deaths related to chronic diseases in China, underscoring the urgent need for effective pharmacological solutions.

MAFLD, with an estimated global prevalence of 32.4%, is closely linked to obesity, affecting a substantial proportion of those with excessive weight. In China, MAFLD has become more prevalent than viral hepatitis, causing concern among healthcare professionals. Addressing this condition involves a multipronged approach, combining lifestyle changes with pharmacological interventions, to enhance life quality and health outcomes.

Innovent is at the forefront of biopharmaceutical innovation, with mazdutide representing one of many initiatives aimed at making high-quality medical treatments accessible to a global audience. The company's commitment to developing pioneering therapies for challenging diseases continues to drive advancements in healthcare.