A Phase 3 Randomized, Double-blind, Placebo-controlled Study to Evaluate the Impact of Maridebart Cafraglutide on Cardiovascular Outcomes in Participants With Atherosclerotic Cardiovascular Disease and Overweight or Obesity

The primary objective of this trial is to demonstrate that maridebart cafraglutide is superior to placebo when given as an adjunct to standard of care with respect to reducing cardiovascular (CV) morbidity and mortality.

开始日期2025-07-29

申办/合作机构

Amgen, Inc.

NCT07037459

/ Not yet recruiting临床3期

A Phase 3 Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Maridebart Cafraglutide on Mortality and Morbidity in Participants Living With Heart Failure With Preserved or Mildly Reduced Ejection Fraction and Obesity (MARITIME-HF)

This study will examine if maridebart cafraglutide as an adjunct to standard of care will lead to a reduction in heart failure (HF) events such as HF hospitalizations and urgent HF visits, cardiovascular (CV) deaths and improvement in HF symptoms in participants with HF with preserved ejection fraction (HFpEF) and HF with mildly reduced ejection fraction (HFmrEF) who are obese. This is a phase 3, global, multicenter, 2-part study with a double-blind period and an open-label extension (OLE). The study is event-driven, and Part 1 will conclude when approximately 850 primary endpoint events have occurred.

开始日期2025-07-29

申办/合作机构

Amgen, Inc.

NCT06987695

/ Not yet recruiting临床3期

A Phase 3 Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy, Safety, and Tolerability of Maridebart Cafraglutide in Adult Participants in Japan Who Have Obesity Disease

The primary objective of this study is to demonstrate that maridebart cafraglutide is superior to placebo for percent change in body weight and proportion of participants with ≥ 5% reduction in body weight.

开始日期2025-06-02

申办/合作机构

Amgen, Inc.

100 项与抗GIPR 抗体（安进）相关的临床结果

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项与抗GIPR 抗体（安进）相关的文献（医药）

2025-05-01·PEPTIDES

Multifunctional incretin peptides in therapies for type 2 diabetes, obesity and associated co-morbidities

Review

作者: Flatt, Peter R ; Bailey, Clifford J ; Conlon, J Michael

Recent studies with peptide-based incretin therapies have focussed mainly on the glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide and the dual agonist tirzepatide that engages receptors for GLP-1 and glucose-dependent insulinotropic polypeptide (GIP). Randomised clinical trials and 'real-world' studies have confirmed the marked glucose-lowering and weight-lowering efficacy of these agents across diverse populations. These include different ethnic groups, young and elderly individuals with and without diabetes and/or overweight or obesity. Recent studies have also confirmed protections against the development and progression of cardiovascular and renal diseases that are additive to the benefits conferred by improved control of blood glucose and body weight. Emerging evidence suggests that incretin therapies could additionally ameliorate fatty liver disease, chronic inflammation, sleep apnea and possibly degenerative bone disorders and cognitive decline. New incretin-based peptide therapies in development include a long-acting glucagon receptor agonist (LY3324954), dual GLP-1/glucagon receptor agonists (survodutide, pemvidutide, mazdutide, G49), triple GLP-1/GIP/glucagon receptor agonists (retatrutide, efocipegtrutide), a combination of semaglutide with the amylin analogue cagrilintide (CagriSema), a unimolecular GLP-1/amylin receptor dual agonist (amycretin), and a GIP receptor antibody with GLP-1 receptor agonism (MariTide). The creation of multi-targeting incretin-based synthetic peptides provides opportunities for improved management of type 2 diabetes and obesity as well as new therapeutic approaches to an expanding list of associated co-morbidities. The aim of the review is to acquaint the reader with developments in the field from 2023 to the present (February 2025).

2025-02-10·JCI Insight

Glucose-dependent insulinotropic polypeptide receptor signaling alleviates gut inflammation in mice

Article

作者: Hammoud, Rola ; Gribble, Fiona M ; Yusta, Bernardo ; Reimann, Frank ; Fishman, Sigal ; Baggio, Laurie L ; Kaur, Kiran Deep ; Efimova, Irina ; Drucker, Daniel J ; Wong, Chi Kin ; Koehler, Jacqueline A ; Varol, Chen ; Advani, Katie E

Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) are gut-derived peptide hormones that potentiate glucose-dependent insulin secretion. The clinical development of GIP receptor-GLP-1 receptor (GIPR-GLP-1R) multiagonists exemplified by tirzepatide and emerging GIPR antagonist-GLP-1R agonist therapeutics such as maritide is increasing interest in the extrapancreatic actions of incretin therapies. Both GLP-1 and GIP modulate inflammation, with GLP-1 also acting locally to alleviate gut inflammation in part through antiinflammatory actions on GLP-1R+ intestinal intraepithelial lymphocytes. In contrast, whether GIP modulates gut inflammation is not known. Here, using gain- and loss-of-function studies, we show that GIP alleviates 5-fluorouracil-induced (5FU-induced) gut inflammation, whereas genetic deletion of Gipr exacerbates the proinflammatory response to 5FU in the murine small bowel (SB). Bone marrow (BM) transplant studies demonstrated that BM-derived Gipr-expressing cells suppress 5FU-induced gut inflammation in the context of global Gipr deficiency. Within the gut, Gipr was localized to nonimmune cells, specifically stromal CD146+ cells. Hence, the extrapancreatic actions of GIPR signaling extend to the attenuation of gut inflammation, findings with potential translational relevance for clinical strategies modulating GIPR action in people with type 2 diabetes or obesity.

2024-11-01·DIABETES CARE

Efficacy and Safety of GLP-1 Medicines for Type 2 Diabetes and Obesity

Review

作者: Drucker, Daniel J.

The development of glucagon-like peptide 1 receptor agonists (GLP-1RA) for type 2 diabetes and obesity was followed by data establishing the cardiorenal benefits of GLP-1RA in select patient populations. In ongoing trials investigators are interrogating the efficacy of these agents for new indications, including metabolic liver disease, peripheral artery disease, Parkinson disease, and Alzheimer disease. The success of GLP-1–based medicines has spurred the development of new molecular entities and combinations with unique pharmacokinetic and pharmacodynamic profiles, exemplified by tirzepatide, a GIP-GLP-1 receptor coagonist. Simultaneously, investigational molecules such as maritide block the GIP and activate the GLP-1 receptor, whereas retatrutide and survodutide enable simultaneous activation of the glucagon and GLP-1 receptors. Here I highlight evidence establishing the efficacy of GLP-1–based medicines, while discussing data that inform safety, focusing on muscle strength, bone density and fractures, exercise capacity, gastrointestinal motility, retained gastric contents and anesthesia, pancreatic and biliary tract disorders, and the risk of cancer. Rapid progress in development of highly efficacious GLP-1 medicines, and anticipated differentiation of newer agents in subsets of metabolic disorders, will provide greater opportunities for use of personalized medicine approaches to improve the health of people living with cardiometabolic disorders.

249

项与抗GIPR 抗体（安进）相关的新闻（医药）

2025-06-24

·FierceBiotech

Amgen rolls out phase 3 dosing plan for lead obesity candidate after midstage trial sees high discontinuation, vomiting rates

Amgen\'s phase 2 MariTime results showed its candidate can help obesity and diabetes patients lose weight, with the caveat that many patients experienced gastrointestinal side effects.\n While Amgen’s monthly obesity candidate MariTide helped patients lose significant amounts of weight in a phase 2 study, prevalent gastrointestinal side effects are leading the company to use a slower dosing schedule in its late-stage trials.Amgen presented the results of part 1 of its phase 2 MariTide study at the American Diabetes Association\'s (ADA\'s) 85th Scientific Sessions in Chicago on Monday, and the data were simultaneously published in The New England Journal of Medicine (NEJM). The study tested the candidate, a GLP-1 agonist and GIPR antagonist, in patients with obesity as well as those with both Type 2 diabetes and obesity.The drug was shown to prompt weight loss across the board, with those with obesity losing an average of 16.2% of their baseline body weight and those with diabetes and obesity shedding 12.3% of their weight on average. However, when looking at only patients who stayed on treatment over the entire 52-week study period, the results came out to average weight loss of 19.9% and 17% between the two patient groups, respectively. By Week 52, patients\' weight loss had not yet plateaued, indicating the drug\'s potential to trigger further weight loss after one year, Amgen noted in its press release. Early discontinuation due to adverse events occurred with varying frequency across the treatment cohorts, but the trend was most notable in those who took higher doses without going through a dose-escalation process first. Of those with obesity who took different doses of the drug without dose escalation, 12% to 27% stopped their trial regimen early due to gastrointestinal events. In the dose-escalation groups, the discontinuation rates due to gastrointestinal adverse events were lower at up to 7.8%.Nausea and vomiting were both frequently reported adverse events, with the highest rates of vomiting (92%) occurring in those with obesity treated with 420 mg every eight weeks and the lowest (43%) reported in the four-week dose-escalation obesity cohort, according to the NEJM data.The gastrointestinal events were mainly limited to patients\' initial dosing, Amgen noted. Either way, the data—and results from a phase 1 pharmacokinetics low-dose initiation study—“shaped our Phase 3 MARITIME program,” the company’s R&D head, Jay Bradner, M.D., said in the release. “MariTide\'s monthly or less frequent dosing has the potential to improve adherence and long-term weight control, providing the opportunity to optimize health outcomes for people living with obesity, Type 2 diabetes and related conditions,” Bradner said.Amgen’s recently initiated 72-week phase 3 MariTide studies in weight management will randomize patients to one of three target doses, putting each group at an initial starting dose of 21 mg before they move up to 35 mg and then to 70 mg over an eight-week escalation period. Both of the company\'s recently initiated late-stage studies, Maritime-1 and Maritime-2, have expected readouts in 2027, according to ClinicalTrials.Gov.Although Amgen\'s stock is down about 5% since the ADA presentation, Jefferies analysts believe the phase 3 data will come in “better than expectations.\" Ultimately, they see Amgen\'s offering as a \"player on the market” with solid efficacy and competitive dosing profile, the analysts wrote in a recent note. Meanwhile, Mizuho Securities analyst Salim Syed thinks that the three-step dose escalation \"may still not be enough\" to cut down on vomiting rates in the phase 3, he wrote in a June 24 note. In a separate note, Citi Research analysts point out that while the three-step design should improve on the rate of adverse events, the strategy “detracts from the convenience narrative” of a long-acting injectable. Still, Amgen holds firm that its candidate maintains commercial viability. The dose-escalation process is “quite simple,” the company’s head of obesity, Susan Sweeney, said on a Monday conference call with analysts. After the initial dosing schedule, patients will take a maintainable monthly therapy that has a “particular benefit” to busy primary care physicians, Sweeney added.The company also looks to study the drug in atherosclerotic cardiovascular disease and heart failure, plus begin a phase 3 study in obstructive sleep apnea in 2025. Based on the weight loss results of the phase 2 as well as improvements across several prespecified cardiometabolic measures, Amgen believes MariTide could be the first monthly therapy for Type 2 diabetes, which has been a “longstanding goal in the field of diabetes development,” Bradner added on the call.

临床2期临床3期临床结果临床1期

2025-06-24

·同写意

下一代GLP-1疗法最新进展盘点：来自礼来、诺和诺德、安进……

同写意年度巨献！！大会特设“GLP-1全产业链创新发展”分会，7月25-26日，邀您相聚金鸡湖畔，与5000人一起为中国医药创新“同写意”！第85届美国糖尿病协会（ADA）科学年会已经在美国芝加哥落下帷幕。ADA年会是全球规模最大的糖尿病和代谢疾病学术会议之一，本届年会上，多家生物医药公司汇报了基于胰高血糖素样肽-1（GLP-1）信号通路开发的创新疗法的最新临床试验结果。GLP-1药物是治疗糖尿病和肥胖症的研发热点之一，目前全球已有超过80款相关药物或药物组合进入临床开发阶段，其中多肽疗法仍是主流。在GLP-1药物开发热潮到来之前，药明康德旗下的WuXi TIDES早已围绕多肽药物建立了一体化CRDMO平台，提供所有类型的多肽，包括线性、环状和高度修饰的多肽，以及非天然氨基酸、连接子、毒素和多肽偶联药物的合成服务，支持从药物发现、CMC开发到商业化生产的各个阶段，助力合作伙伴更高效地为患者提供新一代GLP-1疗法。本文将与读者分享在ADA年会上公布的GLP-1药物的最新研发进展。TONACEA01减掉的超过90%是脂肪！组合疗法2期临床结果公布研究人员公布了礼来公司（Eli Lilly and Company）开发的在研疗法bimagrumab与诺和诺德公司（Novo Nordisk）的GLP-1药物Wegovy（司美格鲁肽）联用，治疗肥胖症的2b期临床试验BELIEVE的最新结果。Bimagrumab是一款潜在“first-in-class"的单克隆抗体，靶向激活素2型受体（ActRII）。ActRII是在脂肪和肌肉细胞中都表达的激活素受体。ActRII受体激活可引发肌肉萎缩并促进脂肪组织中脂肪的堆积。通过阻断该通路，有望在减少脂肪的同时，改善患者的肌肉组成。试验数据显示，接受bimagrumab/Wegovy组合疗法治疗的受试者在72周后体重平均降低22.1%。值得注意的是，丢失的体重中92.8%源于脂肪组织减少。与单药治疗相比，该组合在减少腹部脂肪和炎症相关生物标志物方面也显示出更显著的疗效。TONACEA02体重减轻约20%，安进MariTide完整2期结果发布安进公司（Amgen）今日公布了其在研药物MariTide（maridebart cafraglutide，前称AMG 133）2期临床试验第一部分的完整结果。MariTide是一款潜在“first-in-class”的在研抗体多肽偶联药物，在靶向胃抑制肽受体（GIPR）的单克隆抗体的特定位点上偶联了两个GLP-1类似物，在激活GLP-1受体的同时抑制GIPR。它可通过皮下注射每月或更低频率给药。相关研究结果同时发表于《新英格兰医学杂志》。在2期研究中，MariTide在无2型糖尿病的肥胖人群中实现了最高约20%的平均体重减轻，而安慰剂组为2.6%；在患有糖尿病的肥胖人群中，MariTide组的体重平均减轻最高可达约17%，而安慰剂组仅为1.4%。在第52周时，体重减轻仍未出现平台期，显示出进一步减重的潜力。除了显著的减重效果外，MariTide还在患有糖尿病的肥胖人群中实现了最高达2.2个百分点的糖化血红蛋白（HbA1c）持续且显著下降。体重下降还伴随着一系列心血管代谢指标的改善，包括腰围、血压、高敏C反应蛋白（hs-CRP）及部分血脂参数的改善。▲MariTide的2期临床试验主要疗效结果（图片来源：参考资料[7]）TONACEA03礼来口服GLP-1激动剂3期结果，登《新英格兰医学杂志》礼来公司公布了ACHIEVE-1研究的详细结果。这项3期临床试验评估了orforglipron在仅通过饮食和锻炼控制血糖仍不理想的2型糖尿病成人患者中的安全性与有效性。新闻稿指出，orforglipron是首款完成3期临床试验的口服小分子（非肽类）GLP-1受体激动剂，在服用过程中不受进食与饮水的限制。在第40周时，orforglipron的3种剂量（3 mg、12 mg、36 mg）均达到主要终点，即在降低HbA1c方面优于安慰剂。此外，12 mg和36 mg剂量在体重减轻方面也表现出具有临床意义和统计学显著性的优势。研究显示，orforglipron的安全性特征与已有GLP-1药物相似，最常见的不良事件为胃肠道相关反应。相关结果已在ADA科学年会上公布，并同步发表于《新英格兰医学杂志》。在研究中，orforglipron在第40周达到主要终点，与安慰剂相比，其HbA1c下降幅度为1.3至1.6个百分点。在关键性次要终点方面，最多达76.2%的orforglipron受试者实现了ADA设定的治疗目标HbA1c＜7个百分点；66.0%的受试者达到HbA1c≤6.5个百分点；25.8%的受试者达到HbA1c＜5.7个百分点，即正常HbA1c范围。在另一项关键性次要终点中，接受最高剂量orforglipron治疗的受试者平均减重16.0磅（7.9%）。更长期的研究（如ATTAIN研究）将进一步全面评估orforglipron在肥胖治疗中的安全性与疗效。Orforglipron是一种每日一次的在研口服小分子GLP-1受体激动剂。它由Chugai Pharmaceutical发现，并于2018年授权给礼来公司。目前，礼来正开展orforglipron治疗2型糖尿病，以及治疗肥胖或超重成人患者的3期研究。TONACEA04诺和诺德amycretin早期临床结果登《柳叶刀》，直接进入3期临床试验诺和诺德公司宣布，在研创新肥胖治疗药物amycretin的两项早期临床试验结果在《柳叶刀》杂志上发布。Amycretin是诺和诺德正在研发的一种单分子长效GLP-1和胰淀素受体激动剂，拟用于治疗成人超重或肥胖人群，以及2型糖尿病患者。皮下注射amycretin的1b/2a期试验结果显示，治疗伴发不良事件（TEAEs）多数为轻度或中度，其发生频率呈剂量依赖性升高。最常见的不良事件为胃肠道相关症状。与安慰剂相比，接受amycretin治疗的受试者在研究的所有剂量范围内均观察到更显著的体重下降。接受最高剂量（60 mg）治疗的受试者在36周治疗后体重平均减轻幅度可达24.3%，而安慰剂组仅为1.1%。这一研究结果支持继续探索amycretin在减重方面的潜在疗效。已发表的口服amycretin的1期研究结果显示，最常见的不良事件为胃肠道症状以及食欲下降，且在较高剂量组中更为常见。接受治疗的受试者在所有剂量组中均显示出明显优于安慰剂组的体重减轻效果。探索性分析显示，每日口服100 mg amycretin的受试者在12周后平均体重减轻幅度为13.1%，而安慰剂组仅为1.2%。基于上述及其他已完成的临床研究结果，并结合监管机构的反馈意见，诺和诺德将推进口服与皮下注射两种剂型的amycretin进入3期临床开发，用于体重管理。TONACEA05体重减轻超13%，先为达生物偏向性GLP-1类似物3期临床结果发布先为达生物在ADA年会上发布了其在研cAMP偏向性GLP-1类似物埃诺格鲁肽（ecnoglutide）注射液的3期临床试验结果。该结果同时在The Lancet Diabetes and Endocrinology上发表。Ecnoglutide的cAMP偏向性可能通过降低GLP-1受体的内化和增强胰岛素的分泌来增强GLP-1受体激动剂的临床效果。在2023年4月5日至2024年6月20日期间，这项3期临床试验中，664人被随机分配接受不同剂量的ecnoglutide或安慰剂治疗。在第40周，体重的最小二乘均值百分比变化分别为：ecnoglutide 1.2毫克组为-9.1%，1.8毫克组为-10.9%，2.4毫克组为-13.2%，而安慰剂组为0.1%。与安慰剂相比，各剂量组的预估治疗差值分别为-9.2%、-11.1%和-13.3%，所有比较的p值均<0.0001。在第40周，体重减少≥5%的受试者比例为：ecnoglutide 1.2毫克组为77%，1.8毫克组为84%，2.4毫克组为87%，而安慰剂组仅为16%。GLP-1药物已在治疗2型糖尿病和肥胖方面展现出卓越疗效。ADA年会上公布的最新进展显示，新一代GLP-1药物正通过多种策略提升疗效、安全性和便捷性。药明康德很高兴能够为多款GLP-1药物赋能。今年摩根大通医疗健康大会的报告指出，2024年，公司赋能的临床阶段GLP-1管线从13个增加到20个。其中包括9个临床期多肽药物和11个临床期小分子药物，积极助力新一代GLP-1药物早日触达患者。展望未来，药明康德将继续秉持“让天下没有难做的药，难治的病”的愿景，依托全球研发基地与生产网络，凭借独特的一体化、端到端CRDMO模式，持续推动新一代GLP-1药物的开发进程，造福全球患者。参考资料：（上下滑动查看更多）[1] Novo Nordisk advances early-stage obesity medication, amycretin, to phase 3 clinical development based on early-phase clinical trial results in people with obesity or excess weight, published in The Lancet. Retrieved June 20, 2025, from https://www.prnewswire.com/news-releases/novo-nordisk-advances-early-stage-obesity-medication-amycretin-to-phase-3-clinical-development-based-on-early-phase-clinical-trial-results-in-people-with-obesity-or-excess-weight-published-in-the-lancet-302487500.html[2] Lilly's oral GLP-1, orforglipron, showed compelling efficacy and a safety profile consistent with injectable GLP-1 medicines, in complete Phase 3 results published in The New England Journal of Medicine. Retrieved June 21, 2025, from https://www.prnewswire.com/news-releases/lillys-oral-glp-1-orforglipron-showed-compelling-efficacy-and-a-safety-profile-consistent-with-injectable-glp-1-medicines-in-complete-phase-3-results-published-in-the-new-england-journal-of-medicine-302487392.html[3] Verdiva Bio to Present New Data Highlighting Once-Weekly Potential of Its Investigational Oral Obesity Candidates at the ADA 85th Scientific Sessions. Retrieved June 21, 2025, from https://www.businesswire.com/news/home/20250620108098/en/Verdiva-Bio-to-Present-New-Data-Highlighting-Once-Weekly-Potential-of-Its-Investigational-Oral-Obesity-Candidates-at-the-ADA-85th-Scientific-Sessions[4] Lilly’s bimagrumab boosts weight and fat loss when added to Novo's Wegovy. Retrieved June 23, 2025, from https://endpoints.news/ada25-lillys-bimagrumab-boosts-weight-and-fat-loss-when-added-to-novos-wegovy/[5] Novo Nordisk A/S: CagriSema 2.4 mg / 2.4 mg demonstrated 22.7% mean weight reduction in adults with overweight or obesity in REDEFINE 1, published in New England Journal of Medicine. Retrieved June 23, 2025, from https://www.novonordisk.com/content/nncorp/global/en/news-and-media/news-and-ir-materials/news-details.html?id=916353[6] RESULTS FROM AMGEN'S PHASE 2 OBESITY STUDY OF MONTHLY MARITIDE PRESENTED AT THE AMERICAN DIABETES ASSOCIATION 85TH SCIENTIFIC SESSIONS. Retrieved June 23, 2025, from https://www.prnewswire.com/news-releases/results-from-amgens-phase-2-obesity-study-of-monthly-maritide-presented-at-the-american-diabetes-association-85th-scientific-sessions-302487811.html[7] Jastreboff et al., (2025). Once-Monthly Maridebart Cafraglutide for the Treatment of Obesity — A Phase 2 Trial. NEJM, DOI: 10.1056/NEJMoa2504214

2025-06-23

·药明康德

编者按：第85届美国糖尿病协会（ADA）科学年会已经在美国芝加哥落下帷幕。ADA年会是全球规模最大的糖尿病和代谢疾病学术会议之一，本届年会上，多家生物医药公司汇报了基于胰高血糖素样肽-1（GLP-1）信号通路开发的创新疗法的最新临床试验结果。GLP-1药物是治疗糖尿病和肥胖症的研发热点之一，目前全球已有超过80款相关药物或药物组合进入临床开发阶段，其中多肽疗法仍是主流。在GLP-1药物开发热潮到来之前，药明康德旗下的WuXi TIDES早已围绕多肽药物建立了一体化CRDMO平台，提供所有类型的多肽，包括线性、环状和高度修饰的多肽，以及非天然氨基酸、连接子、毒素和多肽偶联药物的合成服务，支持从药物发现、CMC开发到商业化生产的各个阶段，助力合作伙伴更高效地为患者提供新一代GLP-1疗法。本文将与读者分享在ADA年会上公布的GLP-1药物的最新研发进展。减掉的超过90%是脂肪！组合疗法2期临床结果公布研究人员公布了礼来公司（Eli Lilly and Company）开发的在研疗法bimagrumab与诺和诺德公司（Novo Nordisk）的GLP-1药物Wegovy（司美格鲁肽）联用，治疗肥胖症的2b期临床试验BELIEVE的最新结果。Bimagrumab是一款潜在“first-in-class"的单克隆抗体，靶向激活素2型受体（ActRII）。ActRII是在脂肪和肌肉细胞中都表达的激活素受体。ActRII受体激活可引发肌肉萎缩并促进脂肪组织中脂肪的堆积。通过阻断该通路，有望在减少脂肪的同时，改善患者的肌肉组成。试验数据显示，接受bimagrumab/Wegovy组合疗法治疗的受试者在72周后体重平均降低22.1%。值得注意的是，丢失的体重中92.8%源于脂肪组织减少。与单药治疗相比，该组合在减少腹部脂肪和炎症相关生物标志物方面也显示出更显著的疗效。体重减轻约20%，安进MariTide完整2期结果发布安进公司（Amgen）今日公布了其在研药物MariTide（maridebart cafraglutide，前称AMG 133）2期临床试验第一部分的完整结果。MariTide是一款潜在“first-in-class”的在研抗体多肽偶联药物，在靶向胃抑制肽受体（GIPR）的单克隆抗体的特定位点上偶联了两个GLP-1类似物，在激活GLP-1受体的同时抑制GIPR。它可通过皮下注射每月或更低频率给药。相关研究结果同时发表于《新英格兰医学杂志》。在2期研究中，MariTide在无2型糖尿病的肥胖人群中实现了最高约20%的平均体重减轻，而安慰剂组为2.6%；在患有糖尿病的肥胖人群中，MariTide组的体重平均减轻最高可达约17%，而安慰剂组仅为1.4%。在第52周时，体重减轻仍未出现平台期，显示出进一步减重的潜力。除了显著的减重效果外，MariTide还在患有糖尿病的肥胖人群中实现了最高达2.2个百分点的糖化血红蛋白（HbA1c）持续且显著下降。体重下降还伴随着一系列心血管代谢指标的改善，包括腰围、血压、高敏C反应蛋白（hs-CRP）及部分血脂参数的改善。▲MariTide的2期临床试验主要疗效结果（图片来源：参考资料[7]）礼来口服GLP-1激动剂3期结果登《新英格兰医学杂志》礼来公司公布了ACHIEVE-1研究的详细结果。这项3期临床试验评估了orforglipron在仅通过饮食和锻炼控制血糖仍不理想的2型糖尿病成人患者中的安全性与有效性。新闻稿指出，orforglipron是首款完成3期临床试验的口服小分子（非肽类）GLP-1受体激动剂，在服用过程中不受进食与饮水的限制。在第40周时，orforglipron的3种剂量（3 mg、12 mg、36 mg）均达到主要终点，即在降低HbA1c方面优于安慰剂。此外，12 mg和36 mg剂量在体重减轻方面也表现出具有临床意义和统计学显著性的优势。研究显示，orforglipron的安全性特征与已有GLP-1药物相似，最常见的不良事件为胃肠道相关反应。相关结果已在ADA科学年会上公布，并同步发表于《新英格兰医学杂志》。在研究中，orforglipron在第40周达到主要终点，与安慰剂相比，其HbA1c下降幅度为1.3至1.6个百分点。在关键性次要终点方面，最多达76.2%的orforglipron受试者实现了ADA设定的治疗目标HbA1c＜7个百分点；66.0%的受试者达到HbA1c≤6.5个百分点；25.8%的受试者达到HbA1c＜5.7个百分点，即正常HbA1c范围。在另一项关键性次要终点中，接受最高剂量orforglipron治疗的受试者平均减重16.0磅（7.9%）。更长期的研究（如ATTAIN研究）将进一步全面评估orforglipron在肥胖治疗中的安全性与疗效。Orforglipron是一种每日一次的在研口服小分子GLP-1受体激动剂。它由Chugai Pharmaceutical发现，并于2018年授权给礼来公司。目前，礼来正开展orforglipron治疗2型糖尿病，以及治疗肥胖或超重成人患者的3期研究。诺和诺德amycretin早期临床结果登《柳叶刀》，直接进入3期临床试验诺和诺德公司宣布，在研创新肥胖治疗药物amycretin的两项早期临床试验结果在《柳叶刀》杂志上发布。Amycretin是诺和诺德正在研发的一种单分子长效GLP-1和胰淀素受体激动剂，拟用于治疗成人超重或肥胖人群，以及2型糖尿病患者。皮下注射amycretin的1b/2a期试验结果显示，治疗伴发不良事件（TEAEs）多数为轻度或中度，其发生频率呈剂量依赖性升高。最常见的不良事件为胃肠道相关症状。与安慰剂相比，接受amycretin治疗的受试者在研究的所有剂量范围内均观察到更显著的体重下降。接受最高剂量（60 mg）治疗的受试者在36周治疗后体重平均减轻幅度可达24.3%，而安慰剂组仅为1.1%。这一研究结果支持继续探索amycretin在减重方面的潜在疗效。已发表的口服amycretin的1期研究结果显示，最常见的不良事件为胃肠道症状以及食欲下降，且在较高剂量组中更为常见。接受治疗的受试者在所有剂量组中均显示出明显优于安慰剂组的体重减轻效果。探索性分析显示，每日口服100 mg amycretin的受试者在12周后平均体重减轻幅度为13.1%，而安慰剂组仅为1.2%。基于上述及其他已完成的临床研究结果，并结合监管机构的反馈意见，诺和诺德将推进口服与皮下注射两种剂型的amycretin进入3期临床开发，用于体重管理。体重减轻超13%，先为达生物偏向性GLP-1类似物3期临床结果发布先为达生物在ADA年会上发布了其在研cAMP偏向性GLP-1类似物埃诺格鲁肽（ecnoglutide）注射液的3期临床试验结果。该结果同时在The Lancet Diabetes and Endocrinology上发表。Ecnoglutide的cAMP偏向性可能通过降低GLP-1受体的内化和增强胰岛素的分泌来增强GLP-1受体激动剂的临床效果。在2023年4月5日至2024年6月20日期间，这项3期临床试验中，664人被随机分配接受不同剂量的ecnoglutide或安慰剂治疗。在第40周，体重的最小二乘均值百分比变化分别为：ecnoglutide 1.2毫克组为-9.1%，1.8毫克组为-10.9%，2.4毫克组为-13.2%，而安慰剂组为0.1%。与安慰剂相比，各剂量组的预估治疗差值分别为-9.2%、-11.1%和-13.3%，所有比较的p值均<0.0001。在第40周，体重减少≥5%的受试者比例为：ecnoglutide 1.2毫克组为77%，1.8毫克组为84%，2.4毫克组为87%，而安慰剂组仅为16%。GLP-1药物已在治疗2型糖尿病和肥胖方面展现出卓越疗效。ADA年会上公布的最新进展显示，新一代GLP-1药物正通过多种策略提升疗效、安全性和便捷性。药明康德很高兴能够为多款GLP-1药物赋能。今年摩根大通医疗健康大会的报告指出，2024年，公司赋能的临床阶段GLP-1管线从13个增加到20个。其中包括9个临床期多肽药物和11个临床期小分子药物，积极助力新一代GLP-1药物早日触达患者。展望未来，药明康德将继续秉持“让天下没有难做的药，难治的病”的愿景，依托全球研发基地与生产网络，凭借独特的一体化、端到端CRDMO模式，持续推动新一代GLP-1药物的开发进程，造福全球患者。Enabling the Development of Next-Generation GLP-1 TherapiesThe 85th Scientific Sessions of the American Diabetes Association (ADA) has concluded in Chicago, USA. As one of the world’s largest academic conferences focused on diabetes and metabolic diseases, this year’s meeting showcased the latest clinical trial results from multiple biopharmaceutical companies, including innovative therapies developed based on the glucagon-like peptide-1 (GLP-1) signaling pathway. GLP-1–based drugs have become a major focus in the treatment of diabetes and obesity. To date, more than 80 related drugs or drug combinations have entered clinical development globally, with peptide-based therapies continuing to dominate the landscape.WuXi TIDES, a unique Contract Research and Development Manufacturing Organization (CRDMO) platform, is an integral part of WuXi AppTec. WuXi TIDES offers our worldwide partners efficient, flexible, and high-quality solutions for the drug development of oligonucleotides, peptides and related synthetic conjugates (“TIDES” drugs).GLP-1 based therapies have already demonstrated remarkable efficacy in treating type 2 diabetes and obesity. New data presented at the ADA meeting suggest that next-generation GLP-1 drugs are further enhancing efficacy, safety, and convenience through diverse innovation strategies. For instance, an oral small-molecule GLP-1 receptor agonist showed significant reductions in glycated hemoglobin (HbA1c) levels and body weight in a Phase 3 clinical trial involving type 2 diabetes patients. Notably, it offers the convenience of oral administration without the need to coordinate with food or water intake.In parallel, several early-stage therapies that simultaneously target GLP-1 and other metabolic or appetite-related pathways have shown promising results in clinical trials. By addressing multiple mechanisms associated with weight regulation, these combination approaches may offer enhanced therapeutic benefits.Another key focus area is improving the quality of weight loss. Combination therapies that pair GLP-1 receptor agonists with agents that help preserve muscle mass are being developed to not only reduce fat tissue but also maintain lean body mass. This strategy could provide more meaningful long-term outcomes and improved quality of life for patients seeking to lose weight.Looking ahead, WuXi AppTec will continue to leverage its global R&D and manufacturing network, along with its unique, fully integrated, end-to-end CRDMO model, to empower the development of next-generation GLP-1 drugs and bring meaningful benefits to patients worldwide.参考资料：[1] Novo Nordisk advances early-stage obesity medication, amycretin, to phase 3 clinical development based on early-phase clinical trial results in people with obesity or excess weight, published in The Lancet. Retrieved June 20, 2025, from https://www.prnewswire.com/news-releases/novo-nordisk-advances-early-stage-obesity-medication-amycretin-to-phase-3-clinical-development-based-on-early-phase-clinical-trial-results-in-people-with-obesity-or-excess-weight-published-in-the-lancet-302487500.html[2] Lilly's oral GLP-1, orforglipron, showed compelling efficacy and a safety profile consistent with injectable GLP-1 medicines, in complete Phase 3 results published in The New England Journal of Medicine. Retrieved June 21, 2025, from https://www.prnewswire.com/news-releases/lillys-oral-glp-1-orforglipron-showed-compelling-efficacy-and-a-safety-profile-consistent-with-injectable-glp-1-medicines-in-complete-phase-3-results-published-in-the-new-england-journal-of-medicine-302487392.html[3] Verdiva Bio to Present New Data Highlighting Once-Weekly Potential of Its Investigational Oral Obesity Candidates at the ADA 85th Scientific Sessions. Retrieved June 21, 2025, from https://www.businesswire.com/news/home/20250620108098/en/Verdiva-Bio-to-Present-New-Data-Highlighting-Once-Weekly-Potential-of-Its-Investigational-Oral-Obesity-Candidates-at-the-ADA-85th-Scientific-Sessions[4] Lilly’s bimagrumab boosts weight and fat loss when added to Novo's Wegovy. Retrieved June 23, 2025, from https://endpoints.news/ada25-lillys-bimagrumab-boosts-weight-and-fat-loss-when-added-to-novos-wegovy/[5] Novo Nordisk A/S: CagriSema 2.4 mg / 2.4 mg demonstrated 22.7% mean weight reduction in adults with overweight or obesity in REDEFINE 1, published in New England Journal of Medicine. Retrieved June 23, 2025, from https://www.novonordisk.com/content/nncorp/global/en/news-and-media/news-and-ir-materials/news-details.html?id=916353[6] RESULTS FROM AMGEN'S PHASE 2 OBESITY STUDY OF MONTHLY MARITIDE PRESENTED AT THE AMERICAN DIABETES ASSOCIATION 85TH SCIENTIFIC SESSIONS. Retrieved June 23, 2025, from https://www.prnewswire.com/news-releases/results-from-amgens-phase-2-obesity-study-of-monthly-maritide-presented-at-the-american-diabetes-association-85th-scientific-sessions-302487811.html[7] Jastreboff et al., (2025). Once-Monthly Maridebart Cafraglutide for the Treatment of Obesity — A Phase 2 Trial. NEJM, DOI: 10.1056/NEJMoa2504214免责声明：本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新

临床2期

100 项与抗GIPR 抗体（安进）相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
2型糖尿病	临床3期	阿根廷	Amgen, Inc.	2025-03-12
2型糖尿病	临床3期	比利时	Amgen, Inc.	2025-03-12
2型糖尿病	临床3期	丹麦	Amgen, Inc.	2025-03-12
2型糖尿病	临床3期	芬兰	Amgen, Inc.	2025-03-12
2型糖尿病	临床3期	瑞士	Amgen, Inc.	2025-03-12
2型糖尿病	临床3期	英国	Amgen, Inc.	2025-03-12
肥胖	临床3期	阿根廷	Amgen, Inc.	2025-03-12
肥胖	临床3期	比利时	Amgen, Inc.	2025-03-12
肥胖	临床3期	丹麦	Amgen, Inc.	2025-03-12
肥胖	临床3期	芬兰	Amgen, Inc.	2025-03-12

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临床结果

适应症

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评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT05056246 (CTgov)	临床1期	-	34	AMG 133 (Japanese Participants: AMG 133 Low Dose)	壓網積衊築製構顧壓願(醖餘網構糧鑰壓醖鑰構) = 願簾膚艱製顧製艱衊鏇憲膚鏇醖遞廠鑰憲餘鑰 (觸遞簾襯範鹽膚膚淵壓, 57.3) 更多	-	2025-02-25
				AMG 133 (Japanese Participants: AMG 133 Medium Dose)	壓網積衊築製構顧壓願(醖餘網構糧鑰壓醖鑰構) = 繭鹽築鹹膚簾鏇願淵遞憲膚鏇醖遞廠鑰憲餘鑰 (觸遞簾襯範鹽膚膚淵壓, 24.1) 更多
NCT05669599 (Corporate Publications) 人工标引	临床2期	肥胖	592	AMG 133 420 mg (Without Type 2 Diabetes)	鹽選範網鹽襯鑰鹽壓鬱(願齋壓鹽壓膚獵壓範製) = Without Type 2 Diabetes: MariTide Demonstrated up to ~20% Average Weight Loss at 52 Weeks Without a Weight Loss Plateau; With Type 2 Diabetes: MariTide Delivered an Impressive up to ~17% Average Weight Loss at 52 Weeks Without a Weight Loss Plateau 願憲膚鹹製襯壓鹹衊糧 (蓋衊淵憲鹹艱憲鬱齋夢 ) 更多	积极	2024-11-26
				Placebo (Without Type 2 Diabetes)
NCT04478708 (Corporate Publications) 人工标引	临床1期	肥胖	75	AMG 133	廠鑰壓遞獵襯鑰積衊簾(簾廠繭選築獵鹹淵鑰蓋) = 簾憲鹽網膚遞選鹹淵餘獵齋膚夢顧鹹積製鹹鑰 (積鏇製鏇夢鏇壓襯願獵 )	积极	2022-11-07
				Placebo	廠鑰壓遞獵襯鑰積衊簾(簾廠繭選築獵鹹淵鑰蓋) = 壓鬱夢鏇夢齋醖願構獵獵齋膚夢顧鹹積製鹹鑰 (積鏇製鏇夢鏇壓襯願獵 )