Innovent Initiates Head-to-Head Phase 3 Trial of Mazdutide vs Semaglutide for Obesity with Fatty Liver Disease
核心洞察
Innovent Biologics (搜索) has dosed the first participant in GLORY-3, a Phase 3 trial comparing mazdutide 9 mg to semaglutide 2.4 mg in Chinese adults with overweight/obesity (搜索) and metabolic dysfunction-associated fatty liver disease (搜索).
The 470-participant study will measure changes in liver fat content and body weight over 48 weeks, building on Phase 2 results where mazdutide showed 73.3% reduction in liver fat and 18.6% weight loss.
As a dual GCG (搜索)/GLP-1 (搜索) receptor agonist, mazdutide may offer enhanced metabolic benefits compared to GLP-1-only drugs for treating MAFLD (搜索), which affects up to 81.8% of people with obesity (搜索) in China.
Innovent Biologics (搜索) has announced the successful dosing of the first participant in GLORY-3, a Phase 3 clinical study comparing its dual glucagon (GCG (搜索)) and glucagon-like peptide-1 (GLP-1 (搜索)) receptor agonist mazdutide against semaglutide in Chinese adults with overweight or obesity (搜索) accompanied by metabolic dysfunction-associated fatty liver disease (搜索) (MAFLD (搜索)).
The multicenter, randomized, open-label study (NCT06884293) will enroll approximately 470 participants with a body mass index (BMI) ≥ 27 kg/m² who also have MAFLD (搜索). Participants will be randomized in a 1:1 ratio to receive either mazdutide 9 mg or semaglutide 2.4 mg. The trial has dual primary endpoints: percentage change in liver fat content as measured by magnetic resonance proton density fat fraction (MRI-PDFF) and percentage change in body weight from baseline to week 48.
Strong Phase 2 Results Support Advanced Development
The GLORY-3 trial builds on promising results from a Phase 2 study in Chinese adults with obesity (搜索) (BMI ≥ 30 kg/m²). After 48 weeks of treatment, mazdutide 9 mg achieved an 18.6% (17.8 kg) placebo-adjusted mean reduction in body weight. More than half (51.2%) of participants in the mazdutide group achieved weight loss of 15% or more, while 34.9% lost 20% or more of their baseline weight.
Particularly relevant to the new GLORY-3 study, participants with baseline liver fat content ≥ 5% experienced a 73.3% reduction in liver fat after 24 weeks of treatment with mazdutide 9 mg. This significant decrease was maintained throughout the 48-week extended treatment period, demonstrating mazdutide's potential effectiveness in reducing both body weight and liver fat.
Addressing a Critical Medical Need
"MAFLD (搜索) is now the most common chronic liver disease in the world and has surpassed viral hepatitis as the leading chronic liver disease in China," said Professor Lixin Guo, Principal Investigator of the study from Peking University People's Hospital. "Obesity (搜索) is a key risk factor, with MAFLD affecting up to 81.8% of people with obesity in China."
The latest Chinese guidelines recommend GLP-1 (搜索) agents such as semaglutide for treating obesity (搜索) and MAFLD (搜索). However, as a dual GCG (搜索)/GLP-1 receptor agonist, mazdutide may offer additional benefits through its glucagon receptor activity.
"Mazdutide enhances lipolysis and fatty acid oxidation by stimulating the GCG (搜索) receptor, offering comprehensive metabolic benefits compared to GLP-1 (搜索) single receptor agonist drugs," explained Dr. Lei Qian, Senior Vice President of Clinical Development at Innovent. "I am very confident that mazdutide will continue to show strong clinical efficacy in the GLORY-3 study, including in weight loss and liver metabolism."
Growing Obesity and MAFLD Burden in China
China has the world's largest population of people with overweight or obesity (搜索), and the obesity rate continues to rise. In 2019, overweight and obesity accounted for 11.1% of deaths related to chronic non-communicable diseases in China, a significant increase from 5.7% in 1990.
MAFLD (搜索) has a global prevalence estimated at around 32.4% and is increasing. In China, it has overtaken viral hepatitis as the leading chronic liver condition, affecting 81.8% of obese individuals. China also has the world's highest incidence of MAFLD in both normal-weight and obese populations.
Treatment goals for MAFLD (搜索) include reducing body weight and waist circumference, improving insulin resistance, preventing and treating metabolic-related syndromes, and reversing fibrosis. For patients with MAFLD and overweight or obesity (搜索), combining lifestyle and pharmacological interventions is considered the most effective strategy.
Expanding Clinical Program for Mazdutide
GLORY-3 is part of Innovent's comprehensive clinical development program for mazdutide. The drug is currently being evaluated in six Phase 3 clinical studies, including:
- GLORY-1: A Phase 3 trial in Chinese participants with overweight or obesity
- GLORY-2: A Phase 3 trial in Chinese participants with moderate-to-severe obesity
- DREAMS-1: A Phase 3 trial in treatment-naïve Chinese patients with type 2 diabetes
- DREAMS-2: A Phase 3 trial comparing mazdutide and dulaglutide in Chinese type 2 diabetes patients with inadequate glycemic control on oral antidiabetic drugs
- DREAMS-3: A Phase 3 trial comparing mazdutide and semaglutide in Chinese patients with type 2 diabetes and obesity
Three of these studies—GLORY-1, DREAMS-1, and DREAMS-2—have already met their primary endpoints. Additionally, Innovent is planning several new clinical studies of mazdutide, including trials in adolescents with obesity (搜索), Chinese participants with moderate-to-severe obstructive sleep apnea and obesity, and studies in metabolic dysfunction-associated steatohepatitis and heart failure with preserved ejection fraction.
Mazdutide currently has two New Drug Applications accepted for review by China's National Medical Products Administration: one for chronic weight management in adults with overweight or obesity (搜索), and another for glycemic control in adults with type 2 diabetes (搜索).
As a mammalian oxyntomodulin analogue, mazdutide may offer benefits beyond those of GLP-1 (搜索) receptor agonists by also activating the glucagon receptor to increase energy expenditure and improve hepatic fat metabolism. In clinical studies, it has demonstrated weight loss and glucose-lowering effects, along with benefits in reducing waist circumference, blood lipids, blood pressure, blood uric acid, liver enzymes, and liver fat content, as well as improving insulin sensitivity.