Chinese astronauts add debris shields to Tiangong space station during 8-hour spacewalk (video)
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A pair of taikonauts have completed their first spacewalk aboard China's Tiangong space station, according to the China Manned Space Agency (CMSA).
Two Shenzhou-20 crewmembers performed the mission's first extravehicular activity (EVA) on Thursday (May 22). The duo worked outside the Chinese low-Earth orbit laboratory for eight hours, wrapping up at 4:49 a.m. EDT (0849 GMT; 4:49 p.m. local time in Beijing). Chinese astronauts Chen Dong and Chen Zhongrui served as the EVA's assigned spacewalkers, while their crewmate Wang Jie assisted from inside Tiangong with mission operators coordinating on Earth.
Dong and Zhongrui exited the space station through the node cabin of the Tianhe module, marking the first time that airlock has been used for an EVA since Tiangong became operational.
This was the 19th time taikonauts aboard Tiangong have conducted an EVA; many of these spacewalks have focused on installing debris shields to the station's exterior. With assistance from the station's robotic arm, Dong and Zhongrui successfully positioned a protective sheet on a designated exterior location on Tiangong. The pair also performed routine station maintenance and equipment inspections.
RELATED STORIES:
— 1,000 days in space! Core module of China's Tiangong space station hits milestone
— China launches Shenzhou 20 astronauts to Tiangong space station (video)
— Spacewalks: How they work and major milestones
The Shenzhou-20 crew arrived at Tiangong on April 24, and are just about one month into their six-month-long mission. The trio replaced China's Shenzhou-19 astronauts, who returned to Earth on April 30.
China has at least one more crewed mission planned for 2025. Shenzhou-21 is expected to launch sometime this fall. The Tiangong space station was completed in 2022 and has a continual occupancy planned for at least the next decade. The station presently consists of three main modules, but allows for China to launch more should they wish to expand the orbiting lab.
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Associated Press
an hour ago
- Associated Press
Multiple Research Results from Innovent's General Biomedicine Pipeline to be Showcased at the ADA 85th Scientific Sessions
SAN FRANCISCO and SUZHOU, China, June 21, 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 oncology, autoimmune, cardiovascular and metabolic, ophthalmology and other major disease areas, announced that multiple exploratory mechanism-of-action (MoA) analyses of mazdutide (investigator-initiated trials) as well as a preclinical study of IBI3030 (PCSK9-GGG antibody-peptide-conjugate) will be showcased at the American Diabetes Association's (ADA) 85th Scientific Sessions. Details are listed below： Title: A novel antibody-peptide conjugate targeting PCSK9, GLP-1R, GCGR, GIPR improves cardiovascular risk markers in preclinical study Abstract Number：1886-LB Presentation Form: Poster Presentation Time: Sunday, June 22, 2025. 12:30 P.M. - 1:30 P.M. CDT Location: Poster Hall (Hall F1) Author: Dr. Decheng Ren, Innovent Biologics IBI3030 is a novel anti-PCSK9 antibody conjugated with peptides targeting GLP-1R, GCGR, and GIPR. Through multi-target synergistic effects, it significantly improves cardiovascular metabolic risk indicators. Mechanistically, the anti-PCSK9 antibody component inhibits LDL receptor degradation, thereby lowering reduce plasma LDL-c levels. Simultaneously, the triple-target agonist peptide activates GLP-1R/GCGR/GIPR receptors, enhancing hepatic fatty acid oxidation capacity, with demonstrates superior efficacy compared to the control. Preclinical studies demonstrate that in multiple models (mice, rats, and non-human primates), IBI3030 significantly reduces LDL-c (p<0.01 vs. baseline) and Lp(a), improves oral glucose tolerance (OGTT) (effective even in GLP-1R knockout mice), reduces body weight, and preserves insulin sensitivity. Additionally, it exhibits excellent safety in non-human primates, with a maximum tolerated dose reaching 50 mg/kg. Furthermore, mazdutide, the fastest-developing dual glucagon (GCG)/glucagon-like peptide-1 (GLP-1) receptor agonist globally, has ignited significant research interest in the scientific community due to its comprehensive metabolic benefits. This year's ADA Annual Meeting featured multiple MoA studies on mazdutide's effects in reducing liver fat, improving fibrosis, and lowering serum uric acid. The following are investigator-initiated studies: Topic: The Dual Glucagon and Glucagon-Like Peptide 1 Receptor Agonist Mazdutide Outbalanced Glucagon-Like Peptide 1 Receptor Agonist Semaglutide Monotherapy in Improving Mice Liver Fat Accumulation Abstract Number: 777-P Presentation Form: Poster Presentation Time: Sunday, June 22, 2025. 12:30 P.M. - 1:30 P.M. CDT Location: Poster Hall (Hall F1) Author: Tianpei Hong, Peking University Third Hospital Liver RNA-sequencing and KEGG enrichment analysis showed that compared with Semaglutide treatment, Mazdutide treatment predominantly activated oxidative phosphorylation and fatty acid degradation pathways. Meanwhile, lipid metabolism-related genes were upregulated in Mazdutide group compared to Semaglutide group. We further screened differentially expressed transcription factors (TF) through the TRRUST database and found that activating transcription factor 3 (Atf3) upregulated in the Mazdutide treatment group might be the functional TF regulating lipid degradation in the liver. The dual GCGR/GLP-1R agonist mazdutide exhibited a better efficacy in weight loss and liver fat accumulation alleviation compared with the GLP-1R agonist semaglutide monotherapy potentially due to its promotion of fatty acid oxidation via transcription factor ATF3. Topic: Mazdutide，a GCG/GLP-1R dual-agonist, alleviates MASH and hepatic fibrosis Abstract Number: 1616-P Presentation Form：Poster Presentation Time: Sunday, June 22, 2025. 12:30 P.M. - 1:30 P.M. CDT Location: Poster Hall (Hall F1) Author: Ling Li, Zhongda Hospital, School of Medicine, Southeast University, With the mice presented NASH and fibrosis phenotypes, Mazdutide decreased body weight, liver weight and hepatic triglyceride levels. Notably, Mazdutide also mitigated hepatic fat accumulation, inflammation, and hepatic fibrosis, compared with a single GLP1R or GCGR agonist. Therefore, Mazdutide alleviates hepatic fibrosis in MASH mice and regulates lipid metabolism as well as the gut microbiota, which may contribute to providing a novel therapeutic method and therapeutic target for MASH Topic: Mazdutide, a Dual GLP-1R/GCGR Agonist, Alleviates Hyperuricemia by Modulating Hepatic Energy and Lipid Metabolism and Inhibiting Purine Pathways Abstract Number: 775-P Presentation Form: Poster Presentation Time: Sunday, June 22, 2025. 12:30 P.M.- 1:30 P.M. CDT Location: Poster Hall (Hall F1) Author: Hongwei Jiang, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology Mazdutide significantly lowers serum uric acid levels in hyperuricemic rats, primarily by enhancing fatty acid oxidation and regulating cellular energy metabolism within hepatocytes. This process suppresses the expression of genes associated with glucose and purine metabolism in the liver, leading to a reduction in the generation and utilization of purine precursors. SnRNA-Seq analysis indicates that mazdutide increases the expression of GCGR in hepatocytes, whereas semaglutide slightly inhibits it. In hyperuricemic rats, the expression of key genes involved in fatty acid oxidation, such as Cpt1a, Fabp1, Apoa1, Acox1, and Acaa1a is significantly reduced. However following Mazdutide treatment, the expression of these genes markedly increases, promoting fatty acid oxidation and improving overall energy metabolism. In contrast, genes associated with fatty acid synthesis, such as Acaca and Fasn, show a significant reduction in expression. Furthermore, after Mazdutide intervention, the expression of genes related to glucose metabolism and purine metabolism, including Pklr, G6pc1, Glul, Gckr, Gk, Nt5e, and Ppat, also experience significant decreases. This shift may reflect a change in cellular metabolism towards more efficient fatty acid oxidation, resulting in reduced the generation and utilization of purine precursors. Compared to Semaglutide, Mazdutide offers more substantial benefits in lowering uric acid levels. Dr. Lei Qian from Innovent Biologics, stated, 'We are delighted to see mazdutide's mechanism exploration studies featured extensively at the ADA conference. The growing body of scientific evidence will further validate mazdutide's differentiated profile as a next-generation GCG/GLP-1 dual receptor agonist, particularly in liver fat and serum urine reduction. Moreover, in the field of cardiovascular and metabolic diseases, Innovent is dedicated to developing next-generation innovative therapies. This includes IBI3030 (PCSK9-GGG), a novel modality with a unique MoA that embodies an innovative 'one-drug, multiple-effects' therapeutic strategy. IBI3030 has the potential to deliver comprehensive therapeutic benefits and meaningfully improve outcomes for more patients worldwide.' *Poster 2-4 are results from investigator-initiated trials (IITs) About Mazdutide (IBI362) Innovent entered into an exclusive license agreement with Eli Lilly and Company (Lilly) for the development and potential commercialization of 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. Currently, Mazdutide has two NDAs accepted for review by NMPA, including for: Mazdutide is currently being evaluated in seven Phase 3 clinical studies, including: Among these, GLORY-1, DREAMS-1, and DREAMS-2 have already met their primary endpoints and the other four studies are currently ongoing. In addition, several new clinical studies of mazdutide are initiated or planned, including: 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 [15/16] products in the market. It has [3/2] new drug applications under regulatory review, 4 assets in Phase 3 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: Innovent does not recommend the use of any unapproved drug (s)/indication (s). 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 Biologics ('Innovent'), are intended to identify certain of such forward-looking statements. The Company 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 the Company 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 the Company'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, the Company's competitive environment and political, economic, legal and social conditions. The Company, the Directors and the employees of the Company 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 materialise or turn out to be incorrect. View original content: SOURCE Innovent Biologics
Yahoo
an hour ago
- Yahoo
Multiple Research Results from Innovent's General Biomedicine Pipeline to be Showcased at the ADA 85th Scientific Sessions
SAN FRANCISCO and SUZHOU, China, June 21, 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 oncology, autoimmune, cardiovascular and metabolic, ophthalmology and other major disease areas, announced that multiple exploratory mechanism-of-action (MoA) analyses of mazdutide (investigator-initiated trials) as well as a preclinical study of IBI3030 (PCSK9-GGG antibody-peptide-conjugate) will be showcased at the American Diabetes Association's (ADA) 85th Scientific Sessions. Details are listed below： Title: A novel antibody-peptide conjugate targeting PCSK9, GLP-1R, GCGR, GIPR improves cardiovascular risk markers in preclinical studyAbstract Number：1886-LBPresentation Form: PosterPresentation Time: Sunday, June 22, 2025. 12:30 P.M. - 1:30 P.M. CDTLocation: Poster Hall (Hall F1)Author: Dr. Decheng Ren, Innovent Biologics IBI3030 is a novel anti-PCSK9 antibody conjugated with peptides targeting GLP-1R, GCGR, and GIPR. Through multi-target synergistic effects, it significantly improves cardiovascular metabolic risk indicators. Mechanistically, the anti-PCSK9 antibody component inhibits LDL receptor degradation, thereby lowering reduce plasma LDL-c levels. Simultaneously, the triple-target agonist peptide activates GLP-1R/GCGR/GIPR receptors, enhancing hepatic fatty acid oxidation capacity, with demonstrates superior efficacy compared to the control. Preclinical studies demonstrate that in multiple models (mice, rats, and non-human primates), IBI3030 significantly reduces LDL-c (p<0.01 vs. baseline) and Lp(a), improves oral glucose tolerance (OGTT) (effective even in GLP-1R knockout mice), reduces body weight, and preserves insulin sensitivity. Additionally, it exhibits excellent safety in non-human primates, with a maximum tolerated dose reaching 50 mg/kg. Furthermore, mazdutide, the fastest-developing dual glucagon (GCG)/glucagon-like peptide-1 (GLP-1) receptor agonist globally, has ignited significant research interest in the scientific community due to its comprehensive metabolic benefits. This year's ADA Annual Meeting featured multiple MoA studies on mazdutide's effects in reducing liver fat, improving fibrosis, and lowering serum uric acid. The following are investigator-initiated studies: Topic: The Dual Glucagon and Glucagon-Like Peptide 1 Receptor Agonist Mazdutide Outbalanced Glucagon-Like Peptide 1 Receptor Agonist Semaglutide Monotherapy in Improving Mice Liver Fat AccumulationAbstract Number: 777-PPresentation Form: PosterPresentation Time: Sunday, June 22, 2025. 12:30 P.M. - 1:30 P.M. CDTLocation: Poster Hall (Hall F1)Author: Tianpei Hong, Peking University Third Hospital Liver RNA-sequencing and KEGG enrichment analysis showed that compared with Semaglutide treatment, Mazdutide treatment predominantly activated oxidative phosphorylation and fatty acid degradation pathways. Meanwhile, lipid metabolism-related genes were upregulated in Mazdutide group compared to Semaglutide group. We further screened differentially expressed transcription factors (TF) through the TRRUST database and found that activating transcription factor 3 (Atf3) upregulated in the Mazdutide treatment group might be the functional TF regulating lipid degradation in the liver. The dual GCGR/GLP-1R agonist mazdutide exhibited a better efficacy in weight loss and liver fat accumulation alleviation compared with the GLP-1R agonist semaglutide monotherapy potentially due to its promotion of fatty acid oxidation via transcription factor ATF3. Topic: Mazdutide，a GCG/GLP-1R dual-agonist, alleviates MASH and hepatic fibrosisAbstract Number: 1616-PPresentation Form：PosterPresentation Time: Sunday, June 22, 2025. 12:30 P.M. - 1:30 P.M. CDTLocation: Poster Hall (Hall F1)Author: Ling Li, Zhongda Hospital, School of Medicine, Southeast University, With the mice presented NASH and fibrosis phenotypes, Mazdutide decreased body weight, liver weight and hepatic triglyceride levels. Notably, Mazdutide also mitigated hepatic fat accumulation, inflammation, and hepatic fibrosis, compared with a single GLP1R or GCGR agonist. Therefore, Mazdutide alleviates hepatic fibrosis in MASH mice and regulates lipid metabolism as well as the gut microbiota, which may contribute to providing a novel therapeutic method and therapeutic target for MASH Topic: Mazdutide, a Dual GLP-1R/GCGR Agonist, Alleviates Hyperuricemia by Modulating Hepatic Energy and Lipid Metabolism and Inhibiting Purine PathwaysAbstract Number: 775-PPresentation Form: PosterPresentation Time: Sunday, June 22, 2025. 12:30 P.M.- 1:30 P.M. CDTLocation: Poster Hall (Hall F1)Author: Hongwei Jiang, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology Mazdutide significantly lowers serum uric acid levels in hyperuricemic rats, primarily by enhancing fatty acid oxidation and regulating cellular energy metabolism within hepatocytes. This process suppresses the expression of genes associated with glucose and purine metabolism in the liver, leading to a reduction in the generation and utilization of purine precursors. SnRNA-Seq analysis indicates that mazdutide increases the expression of GCGR in hepatocytes, whereas semaglutide slightly inhibits it. In hyperuricemic rats, the expression of key genes involved in fatty acid oxidation, such as Cpt1a, Fabp1, Apoa1, Acox1, and Acaa1a is significantly reduced. However following Mazdutide treatment, the expression of these genes markedly increases, promoting fatty acid oxidation and improving overall energy metabolism. In contrast, genes associated with fatty acid synthesis, such as Acaca and Fasn, show a significant reduction in expression. Furthermore, after Mazdutide intervention, the expression of genes related to glucose metabolism and purine metabolism, including Pklr, G6pc1, Glul, Gckr, Gk, Nt5e, and Ppat, also experience significant decreases. This shift may reflect a change in cellular metabolism towards more efficient fatty acid oxidation, resulting in reduced the generation and utilization of purine precursors. Compared to Semaglutide, Mazdutide offers more substantial benefits in lowering uric acid levels. Dr. Lei Qian from Innovent Biologics, stated, "We are delighted to see mazdutide's mechanism exploration studies featured extensively at the ADA conference. The growing body of scientific evidence will further validate mazdutide's differentiated profile as a next-generation GCG/GLP-1 dual receptor agonist, particularly in liver fat and serum urine reduction. Moreover, in the field of cardiovascular and metabolic diseases, Innovent is dedicated to developing next-generation innovative therapies. This includes IBI3030 (PCSK9-GGG), a novel modality with a unique MoA that embodies an innovative 'one-drug, multiple-effects' therapeutic strategy. IBI3030 has the potential to deliver comprehensive therapeutic benefits and meaningfully improve outcomes for more patients worldwide." *Poster 2-4 are results from investigator-initiated trials (IITs) About Mazdutide (IBI362) Innovent entered into an exclusive license agreement with Eli Lilly and Company (Lilly) for the development and potential commercialization of 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. Currently, Mazdutide has two NDAs accepted for review by NMPA, including for: Long-term weight management in adults with obesity or overweight. Glycemic control in adults with type 2 diabetes (T2D). Mazdutide is currently being evaluated in seven 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). GLORY-OSA: A Phase 3 trial in Chinese participants with obstructive sleep apnea (OSA) and obesity. DREAMS-1: A Phase 3 trial in treatment-naïve Chinese participants with T2D. DREAMS-2: A Phase 3 trial comparing mazdutide and dulaglutide in Chinese T2D participants with inadequate glycemic control on oral antidiabetic drugs. DREAMS-3: A Phase 3 trial comparing mazdutide and semaglutide in Chinese participants with T2D and obesity. Among these, GLORY-1, DREAMS-1, and DREAMS-2 have already met their primary endpoints and the other four studies are currently ongoing. In addition, several new clinical studies of mazdutide are initiated or planned, including: A Phase 3 trial in adolescents with 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 [15/16] products in the market. It has [3/2] new drug applications under regulatory review, 4 assets in Phase 3 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: Innovent does not recommend the use of any unapproved drug (s)/indication (s). 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 Biologics ("Innovent"), are intended to identify certain of such forward-looking statements. The Company 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 the Company 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 the Company'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, the Company's competitive environment and political, economic, legal and social conditions. The Company, the Directors and the employees of the Company 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 materialise or turn out to be incorrect. View original content: SOURCE Innovent Biologics
Medscape
5 hours ago
- 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."
