A Multicenter, Randomized, Controlled Clinical Study of 3mg Once Every Two Weeks Administration of Efsubaglutide Alfa Injection in Type 2 Diabetes Patients with Poor Glycemic Control After Diet and Exercise Intervention.

This is a study to evaluate the impact and efficacy of Efsubaglutide Alfa injection 3mg QoW on the treatment of type 2 diabetes patients with poor glycemic control after dietary and exercise intervention.
Primary objective:
To evaluate the effect and role of continuous treatment with 3mg of Efsubaglutide Alfa QoW and 1mg of Efsubaglutide Alfa QW for 12 weeks on HbA1c in T2DM patients with poor glycemic control after dietary and exercise intervention.
Secondary objectives:
1. To evaluate the effect of continuous treatment with 3mg of Efsubaglutide Alfa QoW for 12 weeks on glucose variability (change in time in range (TIR) relative to baseline) in T2DM patients with poor glycemic control after dietary and exercise intervention.
2. To evaluate the effect of continuous treatment with 3mg of Efsubaglutide Alfa QoW for 12 weeks on drug exposure (relative to 1mg QW) in T2DM patients with poor glycemic control after dietary and exercise intervention.
3. To evaluate the effect of continuous treatment with 3mg of Efsubaglutide Alfa QoW for 12 weeks on fasting plasma glucose (FPG) in T2DM patients with poor glycemic control after dietary and exercise intervention.

开始日期2024-12-18

申办/合作机构

上海银诺医药技术有限公司

CTR20244074

/ Recruiting临床2期

依苏帕格鲁肽α注射液3mg两周一次给药在饮食和运动干预后血糖控制不佳的2型糖尿病患者中的多中心、随机、对照临床研究

评价依苏帕格鲁肽α注射液3mg两周一次给药（QoW）对饮食和运动干预后血糖控制不佳的2型糖尿病患者（T2DM）治疗的影响和作用。主要目的：在饮食和运动干预后血糖控制不佳的T2DM患者中，评价依苏帕格鲁肽α3mg QoW和1mg QW随机连续治疗12周对HbA1c的影响和作用。次要目的： 1）在饮食和运动干预后血糖控制不佳的T2DM患者中，评价依苏帕格鲁肽α3mg QoW连续治疗12周对患者血糖波动【葡萄糖达标时间百分比（TIR）相对基线的变化】的影响。 2）在饮食和运动干预后血糖控制不佳的T2DM患者中，评价依苏帕格鲁肽α3mg QoW连续治疗12周对药物暴露量的影响（相对 1mg QW）。 3）在饮食和运动干预后血糖控制不佳的T2DM患者中，评价依苏帕格鲁肽α3mg QoW连续治疗12周对空腹血糖（FPG）的影响。

开始日期2024-11-25

申办/合作机构

上海银诺医药技术有限公司

[+1]

NCT06732960

/ Active, not recruiting临床2期

A Randomized, Double-Blind, Placebo-controlled Study of Efsubaglutide Alfa on Weight Management in Subjects With Overweight or Obesity to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics, and Efficacy.

This is a study to evaluate the safety, efficacy, pharmacokinetics and pharmacodynamics of Efsubaglutide Alfa at difference dose range once-weekly in patients with Overweight or Obesity.

开始日期2024-04-21

申办/合作机构

上海银诺医药技术有限公司

[+2]

100 项与依苏帕格鲁肽α 相关的临床结果

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100 项与依苏帕格鲁肽α 相关的转化医学

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100 项与依苏帕格鲁肽α 相关的专利（医药）

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项与依苏帕格鲁肽α 相关的文献（医药）

2022-08-01·European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences

Pharmacokinetic and pharmacodynamic studies of supaglutide in rats and monkeys

Article

作者: Liu, Lin ; Liao, Yijing ; Prud'homme, Gerald J ; Ma, Anran ; Zhang, Li ; Wang, Qinghua ; Wang, Zhihong ; Zhang, Na ; Zhou, Yue

We demonstrated recently that supaglutide, a novel GLP-1 mimetic generated by recombinant fusion protein techniques, exerted hypoglycemic effects in type 2 diabetes db/db mice and spontaneous diabetic monkeys. In this study, we investigated the pharmacokinetics and pharmacodynamics of supaglutide by single subcutaneous and intravenous injection(s) in rats and rhesus monkeys, as well as fourconsecutive subcutaneous injections in monkeys.We found the half-life (t1/2) of supaglutide was 39.7 h and 35.8 h at dosing 0.1 mg/kg upon subcutaneous or intravenous administration respectively, in rhesus monkeys. The plasma supaglutide peaked at 8-10 h, while the plasma drug exposure levels increased with the increase of dose, showing approximately a linear pharmacokinetic characteristic. The elimination kinetics (Ke) were found to be similar between subcutaneous (∼0.025 in rats and ∼0.018 in monkeys) and intravenous administration (0.021 in rats and 0.020 in monkeys), whereas the bioavailability was found to be 31.1% in rats and 63.9% in monkeys. In monkeys, a single dose injection of supaglutide markedly decreased the random blood glucose levels that reaching the maxima effects in 14-16 h, gradually recovered and returned to the baseline level approximately after 72 h. ¹²⁵I-supaglutide was found mainly distributed in the serum and organs rich in blood supply. Urine was found to be the primary excretion route of supaglutide, following by feces, but mostly not in bile.Our results show that supaglutide possess linear pharmacokinetic characteristics associated with prolonged hypoglycemic effects inanimals,suggestinga potential weekly dosing therapeutic reagent for the treatment of type 2 diabetes and metabolic diseases.

2021-02-01·The Journal of endocrinology3区 · 医学

Novel GLP-1 analog supaglutide improves glucose homeostasis in diabetic monkeys

3区 · 医学

Article

作者: Yang, Zhenyan ; Shao, Anna ; Liao, Yijing ; Jiang, Yaojing ; Zeng, Wen ; Zhou, Quanquan ; Tao, Weihong ; Li, Jia ; Huang, Xiaohang ; Zhao, Ying ; Ma, Anran ; Liang, Yinan ; Wang, Qinghua ; Zhang, Li ; Wu, Minglin ; Wang, Zhihong ; Yang, Zunyuan ; Cui, Qiaoli

Glucagon-like peptide 1 (GLP-1) is an insulinotropic hormone and plays an important role in regulating glucose homeostasis. GLP-1 has a short half-life (t1/2 < 2 min) due to degrading enzyme dipeptidyl peptidase-IV and rapid kidney clearance, which limits its clinical application as a therapeutic reagent. We demonstrated recently that supaglutide, a novel GLP-1 mimetic generated by recombinant fusion protein techniques, exerted hypoglycemic and β-cell trophic effects in type 2 diabetes db/db mice. In the present study, we examined supaglutide’s therapeutic efficacy and pharmacokinetics in diabetic rhesus monkeys. We found that a single subcutaneous injection of supaglutide of tested doses transiently and significantly reduced blood glucose levels in a dose-dependent fashion in the diabetic monkeys. During a 4-week intervention period, treatment of supaglutide of weekly dosing dose-dependently decreased fasting and random blood glucose levels. This was associated with significantly declined plasma fructosamine levels. The repeated administration of supaglutide remarkably also decreased body weight in a dose-dependent fashion accompanied by decreased food intake. Intravenous glucose tolerance test results showed that supaglutide improved glucose tolerance. The intervention also showed enhanced glucose-stimulated insulin secretion and improved lipid profile in diabetic rhesus monkeys. These results reveal that supaglutide exerts beneficial effects in regulating blood glucose and lipid homeostasis in diabetic rhesus monkeys.

Frontiers in physiology2区 · 医学

Novel GLP-1 Analog Supaglutide Reduces HFD-Induced Obesity Associated with Increased Ucp-1 in White Adipose Tissue in Mice

2区 · 医学

ArticleOA

作者: Bao, Xi ; Wang, Zhihong ; Cui, Qiaoli ; Wan, Yun ; Wang, Qinghua ; Jiang, Dongdong ; Liu, Wenjuan ; Liu, Rui ; Zhang, Xiangyu ; Huang, Jiabao

GLP-1, an important incretin hormone plays an important role in the regulation of glucose homeostasis. However, the therapeutic use of native GLP-1 is limited due to its short half-life. We recently developed a novel GLP-1 mimetics (supaglutide) by genetically engineering recombinant fusion protein production techniques. We demonstrated that this formulation possessed long-lasting GLP-1 actions and was effective in glycemic control in both type 1 and type 2 diabetes rodent models. Here, we investigated the effects of supaglutide in regulating energy homeostasis in obese mice. Mice were fed with high-fat diet (HFD) for 6 months to induce obesity and then subjected to supaglutide treatment (300 μg/kg, bi-weekly for 4 weeks), and placebo as control. Metabolic conditions were monitored and energy expenditure was assessed by indirect calorimetry (CLAMS). Cold tolerance test was performed to evaluate brown-adipose tissue (BAT) activities in response to cold challenge. Glucose tolerance and insulin resistance were evaluated by intraperitoneal glucose tolerance test and insulin tolerance tests. Liver and adipose tissues were collected for histology analysis. Expression of uncoupling protein 1(Ucp1) in adipose tissues was evaluated by Western blotting. We found that supaglutide treatment reduced body weight, which was associated with reduced food intake. Compared to the placebo control, supaglutide treatment improved lipid profile, i.e., significantly decreased circulating total cholesterol levels, declined serum triglyceride, and free fatty acid levels. Importantly, the intervention significantly reduced fatty liver, decreased liver triglyceride content, and concomitantly ameliorated liver injury exemplified by declined hepatic alanine aminotransferase (ALT) and aspartic transaminase (AST) content. Remarkably, supaglutide reduced hepatic lipid accumulation and altered morphometry in favor of small adipocytes in fat. This is consistent with the observation that supaglutide increased tolerance of the mice to cold environment associated with up-regulation of Ucp1 in the inguinal fat. Furthermore, supaglutide improved glucose tolerance, and insulin sensitivity in the obese mice suggesting improved glucose and energy homeostasis. Our findings suggest that supaglutide exerts beneficial effect on established obesity through reducing energy intake and is associated with brown remodeling of white adipose tissue.

项与依苏帕格鲁肽α 相关的新闻（医药）

2025-03-02

·药事纵横

诺和诺德的司美格鲁肽，还能再大卖几年？

2025年2月5号，诺德诺德发布2024年年报，其中司美格鲁肽注射液Ozempic®全球销售额为1203.42亿丹麦克朗（约合168.96亿美金），口服司美格鲁肽Rybelsus®全球销售额为233.01亿丹麦克朗（约合32.71亿美金），减肥版司美格鲁肽Wegovy®全球销售额为582.06亿丹麦克朗（约合81.72亿美金），以上三款产品2024年全球销售额共计2018.49亿丹麦克朗，约合283.39亿美金，而诺德诺德2024年全年销售额为2904.03亿丹麦克朗（约合407.73亿美金），司美格鲁肽的占比高达69.5%。毫无疑问，司美格鲁肽已经成为诺和诺德最炙手可热的一款产品，而这距离Ozempic® 2017年首次获批上市也才过去了仅仅7年。然而在产品生命周期越来越短的今天，司美格鲁肽还能再大卖几年？司美格鲁肽在国内外又面临着哪些挑战？下面我们将详细叙述来自专利悬崖的挑战众所周知，一款热卖的产品一旦失去专利的保护，其市场必然会受到仿制药的强烈冲击。前任“药王”修美乐（Humira）就是非常经典的例子。在专利到期前的5年时间内，修美乐的年销售额一直稳定在200亿美金上下，随着2022年底专利到期，2023年包括Amgen、Sandoz以及Samsung等10款仿制药全部涌入美国市场，而美国又是修美乐的主要市场，根据Abbvie的年报我们可以看到，由于受到仿制药的冲击，修美乐2023年与2024年销售额分别降到了144亿美金与89.93亿美金。照此趋势推测，2025年修美乐的销售数据将更加惨淡。目前司美格鲁肽三款产品虽然都处于专利保护期内，但根据诺和诺德年报可以看到，其中国专利最早将于2026年到期，而2024年司美格鲁肽三款产品在中国的销售额为64.69亿丹麦克朗，约合66亿人民币，如此一大块“蛋糕”必然会引起国内药企的争夺。根据我国药监局CDE公布的数据，国内目前已经有6家药企对司美格鲁肽原料药进行了备案登记，分别为苏州天马医药、江苏诺泰澳赛诺、湖北健翔生物、浙江湃肽生物、海南中和药业以及齐鲁制药。除此之外也有多家公司宣布在司美格鲁肽原料药的生产过程取得重大进展。如北京铭研医药近日宣布通过对司美格鲁肽传统工艺技术进行创新性改进，成功实现百公斤级合成产能；丽珠集团在2024年的公告中提及，其新北江制药的司美格鲁肽原料药生产线已建成，具备年产原料药300公斤的生产能力；美药星制药公告称将投资2000万元，建成年产达600kg司美格鲁肽原料药生产线等。除了原料药之外，国内在司美格鲁肽制剂方面更是硝烟弥漫。截止撰稿日期，国内已有4家企业向CDE提交了司美格鲁肽注射液的上市申请，分别是九源基因、丽珠集团、齐鲁制药以及珠海联邦。申报路径方面，九源基因、丽珠集团、珠海联邦均按照3.3类生物类似药申报，齐鲁制药则按2.2类化药申报。其中九源基因于2024年4月2号递交了司美格鲁肽注射液的上市申请并获受理，为国内首家，但遗憾的是，根据2024年12月31日药品通知件送达信息显示，九源基因的司美格鲁肽注射液未获批准上市。但需要注意的是，这次未获批的只是九源基因申报的6个规格中的其中两个，另外4个规格仍在正常的审评审批中。而除了上述4家企业，目前也有多家药企的司美格鲁肽注射液处于临床阶段，包括太极集团、海南中和药业、山东新时代、中山万汉制药等。可以预想，等到2026年司美格鲁肽在国内专利到期，将会有大量仿制药上市，分割其国内市场份额。来自其他多肽的挑战目前，司美格鲁肽注射液在全球最大的竞争对手毫无疑问是礼来的替尔泊肽。该化合物的两款产品Mounjaro与Zepbound分别于2022年5月与2023年11月获美国FDA批准上市，虽然这两款产品的上市时间较短，但根据礼来发布的2024年年报可以看到，Mounjaro全年销售额为115.40亿美金，与去年相比上涨124%；Zepbound全年销售额为49.25亿美金，两款产品的合计年销售额已达164.65亿美金。同时，为了降低自费患者每月的用药费用，礼来公司于2025年2月25号宣布推出7.5mg与10mg Zepbound单剂量西林瓶包装，而早在2024年8月礼来就推出了2.5mg与5mg Zepbound单剂量西林瓶包装，如此一来，2.5mg规格的Zepbound每月花费可降低至349美金，而10mg规格每月也仅需699美金。如此低价优惠，外加上更为强大的减肥效果，未来毫无疑问会进一步渗透司美格鲁肽注射液的市场份额。司美格鲁肽注射液在国内同样面临着各种挑战，2025年1月26号，国家药监局发布公告称，批准上海银诺医药申报的依苏帕格鲁肽α注射液（商品名：怡诺轻）上市，用于成人2型糖尿病患者的血糖控制。2月11日，依苏帕格鲁肽α开出了全国首张处方。依苏帕格鲁肽α是国内首个拥有自主知识产权的人源超长效GLP-1受体激动剂，其半衰期长达204小时，是目前全球已上市GLP-1药物中半衰期最长的产品，药频次为每周一次，甚至有望实现每两周给药一次。从国内某大型零售平台可以看到，其1mg/0.5ml与3mg/0.5ml规格每盒（2支装）价格分别在540与1400人民币左右，每个月花费分别在1080与2800人民币。除了银诺的依苏帕格鲁肽α注射液，国内也有多款自主研发的产品进入申报上市以及后临床阶段，如先为达生物的伊诺格鲁肽（Ecnoglutide ，XW003），已于2024年12月17日向CDE递交了新药上市申请。伊诺格鲁肽注射液是一种具有cAMP偏向性的新型长效GLP-1类似物，能激活cAMP信号传导，减少β-抑制蛋白（β-arrestin）介导的内吞和脱敏，从而达到更好血糖控制和体重减轻的效果；信达生物与礼来公司合作开发的GLP-1R/GCGR激动剂玛仕度肽，目前已完成了2项三期临床，据信达估计，其减重和2型糖尿病适应症预计分别将在2025年上半年和下半年获批上市；除此之外，恒瑞医药HRS9531、翰森制药HS-20094、博瑞医药BGM0504等均处在临床三期阶段。来自口服小分子的挑战在讨论口服小分子GLP-1R产品之前，我们先看几条重磅新闻： 2023年11月，阿斯利康以1.85亿美金首付款+最高18.25亿美金里程碑付款，获得中国公司诚益生物的一款口服小分子GLP-1R中国以外的所有地区的独家权益 2023年12月，罗氏公司斥巨资31亿美金收购Carmot Therapeutics，其关键资产之一便是口服GLP-1R小分子产品CT-996 2024年5月，恒瑞医药将三款GLP-1R产品HRS-7535（小分子）、HRS-9531（多肽）以及HRS-4729大中华区以外的独家权益打包转让给美国Hercules公司，为此Hercules将向恒瑞医药支付首付款和近期里程碑款1.1亿美金，总交易额超60亿美金。 2024年12月，翰森制药宣布将临床前口服小分子GLP-1受体激动剂HS-10535的全球权益授权给默沙东，为此默沙东需支付1.12亿美金预付款+最高19亿美金里程碑付款，及一定比例的销售分成，协议总金额高达20.12亿美金毫不夸张的说，一旦口服小分子GLP-1R产品上市，将完全颠覆目前GLP-1R的市场格局。因为与注射相比，口服更加方便，不但可提高患者的用药依从性，而且不存在生物利用度问题，同时口服司美格鲁肽面临的价格昂贵和产能不足的问题也迎刃而解。目前全球领域有两款口服GLP-1R小分子最为引人注意，其中全球进度最快的为礼来公司的Orforglipron，目前已顺利完成二期临床进入三期临床阶段，最早将于2026年初获批上市，其二期临床数据显示，受试组患者体重降幅在8.6%至12.6%之间，而安慰剂组仅为2.0%。36周时，受试组体重降幅达到9.4%至14.7%，达到主要和次要临床终点；另一款产品为歌礼药业的ASC30，既可每月一次皮下注射，也可每日口服一次，同时，其在动物模型中的数据支持更低频率口服给药，或可达一周一次。受此消息影响，歌礼药业盘中大涨，最高涨幅达36%。除此之外，辉瑞、华东医药、硕迪生物、海思科等在此领域也均有布局。 2025年2月5日，诺和诺德发布了2025年16 – 24%的增长预测，相比于2024年的26%略有降低，或许是考虑了全球对司美格鲁肽的实际需求，以及与礼来之间的竞争等因素。但毫无疑问的是，司美格鲁肽注射液在近1-2年仍会是最炙手可热的GLP-1R药物，具体还能大卖几年，就要看上述竞争对手的市场开拓能力与研发速度了。以上为个人观点，仅供参考药事纵横投稿须知：稿费已上调，欢迎投稿

专利到期上市批准

2025-02-18

·同写意

银诺医药怡诺轻®全球首发仪式在智享生物常熟工厂隆重举行 | 会员动态

抗体药物偶联物医药出海

2025-02-18

·智享生物

银诺医药怡诺轻®全球首发仪式在智享生物常熟工厂隆重举行

抗体药物偶联物医药出海上市批准

100 项与依苏帕格鲁肽α 相关的药物交易

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研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
2型糖尿病	中国	上海银诺医药技术有限公司	2025-01-24

未上市

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
肥胖	临床2期	中国	广州银诺医药集团股份有限公司	2024-04-21
非酒精性脂肪性肝炎	临床2期	美国	上海银诺医药技术有限公司	-

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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


NCT04998032 (EASD2024) 人工标引	临床2期	2型糖尿病	120	Efsubaglutide Alfa 1 mg + metformin	製顧獵鏇衊鹽蓋網積顧(築夢齋夢廠鬱廠顧壓憲) = 夢觸窪鏇蓋觸襯簾衊憲網膚糧遞齋齋簾齋鏇膚 (範窪選淵膚壓獵夢醖鑰, -1.38 ~ -0.82) 更多	积极	2024-09-09
				Efsubaglutide Alfa 3 mg + metformin	製顧獵鏇衊鹽蓋網積顧(築夢齋夢廠鬱廠顧壓憲) = 齋齋壓觸願齋顧網選齋網膚糧遞齋齋簾齋鏇膚 (範窪選淵膚壓獵夢醖鑰, -1.70 ~ -1.16) 更多
NCT05694221 (ADA2024) 人工标引	临床1期	-	32	Supaglutide+digoxin	顧鹹願獵糧顧鑰蓋壓製(選襯獵鬱廠鑰鹹範築廠) = the coadministration of supa injection had no effect on the AUC0-last of digoxin, a reduction in Cmax by about 24%, and an increase in the AUC0-inf by about 15% compared with that of the digoxin administration alone. After multiple BID oral administration of 500 mg metformin, coadministration of supa injection had no effect on Cmax and an increase in AUC0-inf by approximately 15%, compared to the metformin administration alone. 築築齋廠構襯選鏇鬱網 (窪遞製簾鬱簾築築選積 )	积极	2024-06-14
				Supaglutide+metformin hydrochloride
NCT04998032 (EASD2023)	临床3期	2型糖尿病追加 HbA1c	344	Supaglutide 3 mg	獵鹽醖壓鏇鹹顧醖製構(遞繭網構窪範網遞壓築) = 遞繭鬱鑰膚醖膚淵觸顧構鹹觸淵憲衊鏇鹹齋遞 (鏇願顧壓獵襯膚衊襯選 )	积极	2023-10-03
NCT04998032 (ADA2023)	临床2/3期	2型糖尿病追加	340	Supaglutide 3 mg	廠窪繭繭淵餘窪憲鹹範(繭壓憲遞蓋襯廠鹽鏇顧) = The most common TEAEs with supa were GI symptoms, such as nausea, vomiting, diarrhea and decreased appetite mostly in mild or moderate severity 製鹽鏇憲廠範鬱窪選願 (壓淵獵鑰簾願膚鹹網網 ) 更多	积极	2023-06-20
NCT04994288 (ADA2023)	临床2/3期	2型糖尿病	297	Supaglutide 1 mg	鏇醖糧夢範構鏇簾鑰簾(範艱製窪憲鏇夢鹹膚積) = 鬱繭顧築觸築鬱鑰遞遞夢壓選積網構鬱選餘範 (夢壓鬱壓範鹽膚醖齋鹹 )	积极	2023-06-20
				Supaglutide 3 mg	鏇醖糧夢範構鏇簾鑰簾(範艱製窪憲鏇夢鹹膚積) = 糧積憲鏇窪積衊淵繭壓夢壓選積網構鬱選餘範 (夢壓鬱壓範鹽膚醖齋鹹 )
ADA2022	N/A	-	48	Supaglutide	淵衊壓窪構顧鹹衊選憲(構衊餘繭艱製糧繭壓壓) = 蓋範齋製艱遞壓蓋窪蓋顧繭製窪壓膚艱夢獵積 (衊衊鑰廠鏇壓觸構憲繭 ) 更多	-	2022-06-01