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Medscape
15 hours ago
- Health
- Medscape
Novel GLP-1 Agonist Promotes Safe and Effective Weight Loss
Ecnoglutide, a novel glucagon-like peptide-1 (GLP-1) receptor agonist, was significantly more effective than placebo for inducing weight loss in adults with overweight or obesity, based on data from more than 600 individuals, results of the SLIMMER trial showed. In addition, ecnoglutide significantly improved other key cardiometabolic risk factors including waist circumference, blood pressure, lipid profile, A1c, fasting glucose, insulin level, and uric acid, while concurrently reducing liver fat content, said study author Linong Ji, MD, of Peking University People's Hospital, Beijing, China. "These benefits position ecnoglutide as a compelling therapeutic strategy for managing clinical obesity, especially in the context of metabolic dysfunction and associated steatotic liver disease (MASLD)," he noted. The results of the phase 3 randomized trial were presented here at the American Diabetes Association (ADA) 85th Scientific Sessions and simultaneously published in The Lancet Diabetes & Endocrinology . The new drug is distinct from other GLP-1 receptor agonists in its ability to selectively induce production of cyclic adenosine monophosphate (cAMP). Unlike unbiased GLP-1 therapies, ecnoglutide selectively activates cAMP signaling pathways while minimizing β-arrestin recruitment, which may explain its enhanced effectiveness for body weight reduction and sustained metabolic effects, Ji said in an interview. Weight Loss at All Doses The researchers randomized 664 overweight and obese Chinese adults to a weekly dose of 1.2 mg, 1.8 mg, or 2.4 mg of ecnoglutide or to placebo. The coprimary endpoints were percentage change in body weight and proportion of individuals with a reduction of 5% or more in body weight after 40 weeks. The study population included adults aged 18-75 years with overweight or obesity, defined as a BMI of 28 kg/m² or higher, or 24 kg/m² or higher with at least one weight-related comorbidity (prediabetes, hypertension, hyperlipidemia, MASLD, obstructive sleep apnea syndrome, or weight-bearing joint pain), but without type 1 or 2 diabetes. The mean age of participants was 34.2 years, and half were female. Individuals in the ecnoglutide group had an average body weight loss of 9.1%, 10.9%, and 13.2% from baseline at 40 weeks at doses of 1.2 mg, 1.8 mg, and 2.4 mg, respectively, which was significantly greater at all dose levels than placebo (0.1%) ( P < 0.0001 vs placebo for all doses). In addition, significantly more patients in the ecnoglutide groups lost at least 5% of their body weight at week 40 compared to the placebo group (77%, 84%, 87%, and 16% in the 1.2-mg, 1.8-mg, 2.4-mg, and placebo groups, respectively). A key secondary efficacy endpoint was the percentage of individuals who achieved a body weight loss of at least 5% after 48 weeks; 78% to 93% of participants across the ecnoglutide groups achieved this endpoint, with the greatest changes at the higher doses. Ten individuals across the ecnoglutide groups discontinued the medication because of adverse events, the most common of which were mild-to-moderate gastrointestinal events. Treatment-emergent adverse events occurred in 93% of participants in each of the ecnoglutide groups and in 84% of the placebo group. Clinical Takeaways and Next Steps "Ecnoglutide not only represents a viable competitor in the GLP-1 analog market but also stands out with its potential to address the nonresponse limitations in obesity treatment while providing holistic metabolic benefits," Ji told Medscape Medical News . At least 10% of weight-loss patients fail to achieve clinically significant weight loss of at least 5%, he explained. Possible reasons for the lack of success include genetic polymorphisms, metabolic heterogeneity, treatment compliance, or differential receptor sensitivity, he noted. "Providing alternative treatment options with a high response rate is crucial for individuals nonresponsive to existing therapies," he said. The trial results mark a milestone in obesity therapeutics and are a significant achievement in weight management. "After 48 weeks of treatment, ecnoglutide achieved a 15.4% weight reduction, with 92.8% of patients attaining clinically meaningful weight loss," he emphasized. "Considering the high potency of ecnoglutide" and the safety data, "it might serve as a viable option for individuals who do not achieve sufficient weight reduction with existing GLP-1 receptor agonists at their approved doses or need to achieve a better reduction in body weight," he added. "I am confident and optimistic that we'll see more personalized treatment regimens for obesity." Looking ahead, patients in the ecnoglutide 1.8-mg and 2.4-mg groups continued to have weight loss at week 48 without reaching a plateau, indicating that even greater weight loss might be possible with extended ecnoglutide treatment in studies of longer duration, Ji told Medscape Medical News . "To confer the added clinical advantage, a study comparing the clinical effects of a biased GLP-1 analog with those of a pharmacokinetically-matched but balanced GLP-1 analog would be needed," he said. In an accompanying editorial, Tricia M-M Tan, PhD, of Imperial College, London, UK, wrote: "The development of biased GLP-1 receptor agonists has been met with enthusiasm from the pharmaceutical industry, but does this design feature really confer any added clinical advantage?" She agreed with Ji that a comparative study of "a biased GLP-1 analog with those of a pharmacokinetically-matched but balanced GLP-1 analog" is needed. "Only then will the clinical role of this design feature be clear," she said. However, "the clinical results from ecnoglutide are likely to be generalizable to other populations," given that the effects of GLP-1 analogs are similar when tested in patients of various ethnicities, she said, adding this may increase the global availability of GLP-1 treatments. Refining Molecules to Enhance Efficacy, Reduce Side Effects Although current therapies represent potent, effective options for obesity-modifying treatment, they have limitations, with heterogeneity of responses in terms of potency and tolerability, said Andrew Kraftson, MD, a specialist in endocrinology and internal medicine at the University of Michigan, Ann Arbor, in an interview. "Ecnoglutide continues the trend to refine these molecules to enhance efficacy and reduce side effects," he said. "When these types of peptides interact with cells, they activate certain receptors and generate a signal cascade that promotes the desired effects. However, the less specific the 'message', the less potent the signal. Additionally, side effects can be a result of the less-controlled message," he noted. As with tirzepatide, ecnoglutide was developed to produce a "biased" signal with the intent to provide greater control of the signal/message to increase the odds of weight control and reduce the odds of side effects, he explained. Although the current study was not a head-to-head comparison with other incretin mimetics, the similarity in weight loss efficacy to tirzepatide, a dual GLP-1/glucagon insulinotropic peptide agonist (GIP), was interesting and supports the biasing effect of the molecular manipulation as an effective strategy to refine incretin therapy, Kraftson told Medscape Medical News . From a clinical standpoint, the trend towards refining weight management therapy will benefit patients by expanding their options, said Kraftson. "It may also help us address the observed heterogeneity in clinical response we see in our patients and bring us closer to personalized medicine," he said. The current study's limitations, as acknowledged by the researchers, include the relatively short time period, small sample size, and lack of head-to-head comparison, said Kraftson. Additionally, the study differs from clinical practice in its dose escalation, he said. In practice, "we are not trying to get patients to a certain dose, we are trying to find the lowest, most tolerable, and sufficiently effective dose to achieve health goals; therefore, we may determine that dose titration needs to happen more slowly and/or that a low(er) dose may be sufficiently effective," he told Medscape Medical News . "The adverse event data for common gastrointestinal issues could potentially be better in clinical practice if mitigation strategies are employed," he said. "I would like to see future studies that go beyond finding the relative efficacy of doses to reporting on effective strategies for patient-dose matching."
Yahoo
26-05-2025
- Health
- Yahoo
Phase 3 Clinical Study of Mazdutide in Chinese Adults with Overweight or Obesity (GLORY-1) Published in The New England Journal of Medicine (NEJM)
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 [ 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 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. (accessed Jan 10, 2021). View original content: SOURCE Innovent Biologics
Yahoo
26-05-2025
- Health
- Yahoo
Phase 3 Clinical Study of Mazdutide in Chinese Adults with Overweight or Obesity (GLORY-1) Published in The New England Journal of Medicine (NEJM)
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 [ 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 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. (accessed Jan 10, 2021). View original content: SOURCE Innovent Biologics Sign in to access your portfolio
Associated Press
05-03-2025
- Health
- Associated Press
HighTide Therapeutics Announces Publication of Phase 2 Study of Berberine Ursodeoxycholate for the Treatment of Type 2 Diabetes Mellitus in JAMA Network Open
ROCKVILLE, MD and SHENZHEN - March 4, 2025 ( NEWMEDIAWIRE) - HighTide Therapeutics, Inc. ( a clinical stage biopharmaceutical company specializing in the development of multifunctional multi-targeted therapies for chronic liver and metabolic diseases, today announced that data from the Phase 2 proof-of-concept study evaluating berberine ursodeoxycholate (HTD1801) for the treatment of type 2 diabetes mellitus (T2DM) was published online in JAMA Network Open. The publication reports results of the randomized, placebo-controlled 12-week study to assess efficacy, safety and tolerability of HTD1801 compared to placebo in patients with T2DM. The trial achieved its primary endpoint by demonstrating a statistically significant and superior reduction in HbA1c at week 12 with HTD1801 versus placebo. A majority of patients treated with HTD1801 achieved target HbA1c <7%. Further, results show therapeutic benefit of HTD1801 on LDL and total cholesterol, markers of liver injury and systemic inflammation. In this study, HTD1801 was well tolerated with no treatment-related serious adverse events observed. These findings are being confirmed in ongoing Phase 3 studies. 'We are encouraged by the results of this Phase 2 study. The study provides evidence that HTD1801 can treat the core aspects of metabolic syndrome, with potential to provide a spectrum of therapeutic effects that appear to address comorbid conditions that exacerbate disease and worsen prognosis of patients with T2DM,' said Dr. Linong Ji, Professor of Medicine at Peking University, Director of Peking University Diabetes Center and Director of the Department of Endocrinology and Metabolism, Peking University People's Hospital, in Beijing, China. 'Based on these positive findings, we are continuing to advance the clinical development of HTD1801 in our ongoing Phase 3 T2DM program with topline results expected in the first half of this year,' said Dr. Liping Liu, CEO of HighTide Therapeutics. About JAMA Network Open Journal JAMA Network Open is an international, peer-reviewed, open access, general medical journal that publishes research on clinical care, innovation in health care, health policy, and global health across all health disciplines and countries for clinicians, investigators, and policy makers. JAMA Network Open is a member of the JAMA Network, a consortium of peer-reviewed, general medical and specialty publications. About Berberine Ursodeoxycholate (HTD1801) Berberine ursodeoxycholate (HTD1801) is an orally delivered, gut-liver anti-inflammatory metabolic modulator being developed for the treatment of metabolic and digestive diseases. HTD1801, an ionic salt of berberine and ursodeoxycholate, is a new molecular entity with unique dual mechanisms of action, including AMP kinase activation and NLRP3 inflammasome inhibition. These two key mechanistic pathways have been associated with improvements in glucose metabolism, insulin resistance, lipid metabolism, and hepatic inflammation, potentially providing a comprehensive treatment platform for the multifaceted nature of complex metabolic diseases such as T2DM. About HighTide Therapeutics HighTide Therapeutics, Inc. (Stock Code: is a globally integrated biopharmaceutical company focusing on the discovery and development of first-in-class multifunctional multi-targeted therapies with poly-indication potential across multiple metabolic and digestive diseases with significant unmet medical needs. The Company is currently developing several clinical assets and holding global intellectual property rights, advancing multiple mid-to-late-stage clinical trials including therapy for metabolic dysfunction-associated steatohepatitis (MASH), type 2 diabetes mellitus (T2DM), severe hypertriglyceridemia (SHTG) and primary sclerosing cholangitis (PSC). Berberine ursodeoxycholate (HTD1801), the Company's lead drug candidate, received Fast Track designation from the United States Food and Drug Administration for both MASH and PSC and Orphan Drug designation for PSC. HTD1801 has been included in the National Major New Drug Innovation Program under the 13th Five-Year Plan for Major Technology Project in China.
