Phase 3 Clinical Study of Mazdutide in Chinese Adults with Overweight or Obesity (GLORY-1) Published in The New England Journal of Medicine (NEJM)

Yahoo

26-05-2025

SAN FRANCISCO and SUZHOU, China, May 26, 2025 /PRNewswire/ -- Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of oncologic, autoimmune, cardiovascular and metabolic, ophthalmologic and other major diseases, announces that the results of a Phase 3 clinical study of mazdutide , a dual glucagon (GCG)/glucagon-like peptide-1 (GLP-1) receptor agonist, in Chinese adults with overweight or obesity (GLORY-1) have been published in The New England Journal of Medicine (NEJM) with a related editorial [https://www.nejm.org/doi/full/10.1056/NEJMoa2411528]. The first authors of this paper are Professor Linong Ji from Peking University People's Hospital and Professor Jiang Hongwei from the First Affiliated Hospital of Henan University of Science and Technology. In addition, Professor Linong Ji and Dr. Lei Qian from Innovent Biologics, served as the co-corresponding authors.
This marks the first time that a clinical study of mazdutide, the world's first dual GCG/GLP-1 receptor agonist submitted for marketing, has been featured in a top-tier, peer-reviewed medical journal. It is also the first time a clinical trial of an innovative metabolic and endocrine therapy developed in China has been published in NEJM, a milestone that highlights China's growing capabilities in drug development and biotechnology innovation. This publication is expected to contribute to the evolving global clinical guidelines for the treatment of overweight and obesity.
Regarding this groundbreaking new study, Professors Vanita R. Aroda of Harvard Medical School and Brigham and Women's Hospital, Boston, and Leigh Perreault of the University of Colorado Anschutz Medical Campus jointly commented that the GLORY-1 trial reveals distinct characteristics in the Chinese population compared to Western populations. Specifically, younger individuals in China exhibit metabolic dysfunction at rates comparable to or even exceeding those in older Western populations. The dual GCG/GLP-1 receptor agonist therapy demonstrated not only significant reductions in body weight and BMI but also comprehensive improvements in obesity-associated systemic health risks. Moreover, they emphasized that obesity interventions in China must adopt differentiated strategies tailored to local population features, with a focus on liver health and lipid management. Given the earlier onset of obesity in China and its heavier societal burden, earlier intervention is critical—and yields greater long-term benefits. For emerging obesity therapies, the experts noted that pharmacological treatments are only one component of a broader strategy. They advocated for synergizing drug therapies with public health policies to build a comprehensive prevention and treatment system, addressing the global obesity epidemic more effectively.
Mazdutide is expected to launch in China this year, with anticipated approvals for weight management and glycemic control. Recognized for its superior weight loss efficacy and comprehensive metabolic benefits, mazdutide has been ranked among FIERCE Pharma's 2025 Top 10 Most Anticipated Drugs.
In the GLORY-1 study, a total of 610 participants with obesity (BMI ≥ 28 kg/m2) or overweight (24 kg/m2 ≤ BMI < 28 kg/m2) with at least one obesity-related comorbidity were enrolled and randomized to receive mazdutide 4 mg, 6 mg, or placebo, administered subcutaneously once weekly for 48 weeks. The co-primary endpoints were the percentage change in body weight from baseline and a weight reduction of ≥5% at week 32.
At baseline, the mean weight was 87.2 kg, and the mean BMI was 31.1 kg/m 2. The study results showed that mazdutide significantly reduced body weight compared to placebo at both 4 mg and 6 mg doses.
Based on the efficacy estimand, the mean percent change from baseline in body weight was −10.97%, −13.38%, and −0.24% at Week 32 and −12.05%, −14.84%, and −0.47% at Week 48 in the mazdutide 4 mg, 6 mg, and placebo groups, respectively. A total of 76.3% of participants in the mazdutide 4 mg group and 84.0% in the mazdutide 6 mg group had a weight reduction of ≥5% at week 32, compared with 10.9% in the placebo group; 37.0% of participants in the mazdutide 4 mg group and 50.6% in the mazdutide 6 mg group had a weight reduction of ≥15% at week 48, compared with 2.1% in the placebo group.
The primary endpoint and all key secondary endpoints of the study showed statistically significant superiority to placebo with p-values < 0.001 (main results as follows).Efficacy Estimand1
Treatment-policy estimand2Mazdutide
4 mg (N=203)
Mazdutide
6 mg (N=202)
Placebo
(N = 205)
Mazdutide
4 mg (N=203)
Mazdutide
6 mg (N=202)
Placebo
(N = 205)
Co-primary endpoints (Week 32)
Percent weight reduction
−10.97%
−13.38%
−0.24%
−10.09%
−12.55%
0.45 %
Achieved a weight reduction ≥5%
76.3 %
84.0 %
10.9 %
73.9 %
82.0 %
10.5 %
Some key secondary endpoints (Week 48)
Percent weight reduction
−12.05%
−14.84%
−0.47%
−11.00%
−14.01%
0.30 %
Achieved a weight reduction ≥5%
73.5 %
82.8 %
11.5 %
71.6 %
81.6 %
10.8 %
Achieved a weight reduction ≥10%
55.2 %
67.9 %
2.9 %
53.5 %
66.7 %
2.6 %
Achieved a weight reduction ≥15%
37.0 %
50.6 %
2.1 %
35.7 %
49.5 %
2.0 %
Waist circumference reduction
−9.48 cm
−10.96 cm
−1.48 cm
−9.12 cm
−10.72 cm
−1.41 cm
1. Efficacy estimand aims to estimate the study treatment effect when participants adhered to the planned treatment regimen.
2. Treatment policy estimand aims to evaluate the efficacy regardless of intercurrent events (early discontinuation of study treatment and initiation of new anti-obesity medication or bariatric surgery).
Mazdutide also significantly reduced blood pressure, blood lipids (total cholesterol, triglycerides, and low-density lipoprotein cholesterol), serum uric acid, transaminase levels, and other cardiovascular and metabolic indicators.
In addition, mazdutide significantly reduced liver fat content.
Among participants with baseline liver fat content ≥ 5%, the mean percent changes in liver fat content from baseline to week 48 were −63.26%, −73.18%, and +8.20% in the mazdutide 4 mg, 6 mg, and placebo groups, respectively;
Among participants with baseline liver fat content ≥ 10%, the mean percent change from baseline in liver fat content to week 48 were −65.85%, −80.24%, and −5.27% in the mazdutide 4 mg, 6 mg, and placebo groups, respectively.
Good overall safety and tolerability of mazdutide were reported.
The overall safety profile of the mazdutide group was consistent with findings from previous studies of mazdutide and aligned with that of other GLP-1 receptor agonists. The most frequently reported treatment-emergent adverse events included nausea, diarrhea, and vomiting, which were mostly mild or moderate in severity.
At Week 48, both the mean change from baseline in heart rate was 2.6 beats per minute in both the mazdutide 4 mg and 6 mg groups. There were no safety signals of increased cardiovascular risk observed throughout the study.
Professor Linong Ji, the Leading Principal Investigator of the Study, Peking University People's Hospital, stated, "For decades, global obesity management guidelines have predominantly relied on data from Caucasian populations, resulting in limited applicability to Asian demographics. Meanwhile, China's overweight/obese population exhibits distinct clinical characteristics and therapeutic needs compared to Western populations, necessitating evidence-based weight management strategies specifically tailored for Chinese patients. For most Chinese patients with overweight or obesity, the recommended weight loss target should be 5%-15% reduction maintained over 3-6 months. Moderate-to-severe obesity patients may require more ambitious goals. The GLORY-1 study, conducted in Chinese populations aligned with these targets, demonstrated promising outcomes: mazdutide achieved >15% weight reduction in nearly half of participants, indicating its efficacy across people living with overweight to severe obesity.
Published in The New England Journal of Medicine, the GLORY-1 study not only signifies international recognition of China's innovative research in endocrine-metabolic disorders but also underscores the pioneering innovation of Chinese biopharmaceutical industry. Mazdutide's successful development will accelerate domestic enterprises' strategic presence in obesity management, enabling comprehensive, personalized solutions for China's overweight/obese population throughout their treatment journey."
Dr. Lei Qian from Innovent Biologics, stated, "Mazdutide is globally first dual GCG/GLP-1 receptor agonist to be approved soon. The publication of its pivotal study GLORY-1 in The New England Journal of Medicine marks a breakthrough in China's drug development in endocrine and metabolic diseases. The study provides robust, high-quality clinical evidence for treating overweight and obesity in Chinese adults and will undoubtedly influence future clinical guidelines, diagnostic criteria, and standards of care. This academic achievement also demonstrates the exceptional clinical research capabilities of Chinese investigators and the solid innovative R&D abilities of Innovent. With mazdutide's imminent approval in China, we look forward to offering an advanced therapeutic option to improve the health and quality of life of individuals living with overweight or obesity. As an innovative pharmaceutical company, Innovent has actively responded to and promoted the goal of 'Healthy China 2030' by advancing science-based weight management through strategic collaborations and cutting-edge medical achievements. "
About Obesity
China has the world's largest population of individuals with overweight or obesity[1], a trend that is likely to rise. Obesity is associated to multiple comorbidities, and is a major contributor to reduced life expectancy and quality of life. In 2019, overweight and obesity accounted for 11.1% of deaths from chronic non-communicable diseases in China, nearly doubling from 5.7% in 1990[2].
Despite the chronic nature of obesity and its need for long-term management, treatment options remain limited. While lifestyle interventions remains the cornerstone of treatment, many patients struggle to achieve or maintain meaningful weight reduction. This underscores the urgent need for safe, effective and sustainable pharmacological interventions.
About Mazdutide (IBI362)
Innovent entered into an exclusive license agreement with Eli Lilly and Company (Lilly) for the development and potential commercialization of OXM3 (also known as mazdutide), a GLP-1R and GCGR dual agonist, in China. As a mammalian oxyntomodulin (OXM) analogue, mazdutide may offer additional benefits beyond those of GLP-1 receptor agonists—such as promoting insulin secretion, lowering blood glucose and reducing body weight—by also activating the glucagon receptor to increase energy expenditure and improve hepatic fat metabolism. Mazdutide has demonstrated excellent weight loss and glucose-lowering effects in clinical studies. It has also shown benefits in reducing waist circumference, blood lipids, blood pressure, blood uric acid, liver enzymes, and liver fat content, as well as improving insulin sensitivity.
Mazdutide currently has two NDAs accepted for review by NMPA, including:
For chronic weight management in adults with overweight or obesity;
For glycemia control in adults with type 2 diabetes.
Mazdutide 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.
GLORY-3: A Phase 3 trial comparing mazdutide and semaglutide in Chinese participants with overweight/obesity and metabolic dysfunction-associated fatty liver disease (MAFLD).
DREAMS-1: A Phase 3 trial in treatment-naïve Chinese patients with T2D.
DREAMS-2: A Phase 3 trial comparing mazdutide and dulaglutide in Chinese T2D patients with inadequate glycemic control on oral antidiabetic drugs.
DREAMS-3: A Phase 3 trial comparing mazdutide and semaglutide in Chinese patients with T2D and obesity.
Among these, GLORY-1, DREAMS-1 and DREAMS-2 studies have all met their endpoints, and other studies are currently ongoing.
In addition, several new clinical studies of mazdutide are planned, including:
A Phase 3 trial in adolescents with obesity.
A Phase 3 trial in Chinese participants with moderate-to-severe obstructive sleep apnea (OSA) and obesity.
New studies in metabolic dysfunction-associated steatohepatitis (MASH) and heart failure with preserved ejection fraction (HFpEF).
About Innovent
Innovent is a leading biopharmaceutical company founded in 2011 with the mission to empower patients worldwide with affordable, high-quality biopharmaceuticals. The company discovers, develops, manufactures and commercializes innovative medicines that target some of the most intractable diseases. Its pioneering therapies treat cancer, cardiovascular and metabolic, autoimmune and eye diseases. Innovent has launched 15 products in the market. It has 3 new drug applications under regulatory review, 4 assets in Phase III or pivotal clinical trials and 15 more molecules in early clinical stage. Innovent partners with over 30 global healthcare companies, including Eli Lilly, Sanofi, Incyte, LG Chem and MD Anderson Cancer Center.
Guided by the motto, "Start with Integrity, Succeed through Action," Innovent maintains the highest standard of industry practices and works collaboratively to advance the biopharmaceutical industry so that first-rate pharmaceutical drugs can become widely accessible. For more information, visit www.innoventbio.com, or follow Innovent on Facebook and LinkedIn.
Statement: (1) Innovent does not recommend the use of any unapproved drug (s)/indication (s).
(2) Ramucirumab (Cyramza) and Selpercatinib (Retsevmo) and Pirtobrutinib (Jaypirca) were developed by Eli Lilly and Company.
Forward-looking statement
This news release may contain certain forward-looking statements that are, by their nature, subject to significant risks and uncertainties. The words "anticipate", "believe", "estimate", "expect", "intend" and similar expressions, as they relate to Innovent, are intended to identify certain of such forward-looking statements. Innovent does not intend to update these forward-looking statements regularly.
These forward-looking statements are based on the existing beliefs, assumptions, expectations, estimates, projections and understandings of the management of Innovent with respect to future events at the time these statements are made. These statements are not a guarantee of future developments and are subject to risks, uncertainties and other factors, some of which are beyond Innovent's control and are difficult to predict. Consequently, actual results may differ materially from information contained in the forward-looking statements as a result of future changes or developments in our business, Innovent's competitive environment and political, economic, legal and social conditions.
Innovent, the Directors and the employees of Innovent assume (a) no obligation to correct or update the forward-looking statements contained in this site; and (b) no liability in the event that any of the forward-looking statements does not materialize or turn out to be incorrect.
References
[1] Pan XF, Wang L, Pan A. Epidemiology and determinants of obesity in China. Lancet Diabetes Endocrinol 2021; 9: 373–92.
[2] Institute for Health Metrics and Evaluation. Global Health Data Exchange. GBD results tool. http://ghdx.healthdata.org/gbd-resultstool (accessed Jan 10, 2021).
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