A Thorough QTc Evaluation of the Effect of Cotadutide on Cardiac Repolarization in Healthy Participants: A Randomized, Double-blind, Placebo-controlled, 3-arm Parallel Study With a Nested Crossover Design for Positive Control With Moxifloxacin Administration

This study will investigate the effect of multiple doses of cotadutide on the cardiac activity (QTc interval) of healthy participants.

开始日期2023-01-03

申办/合作机构

AstraZeneca PLC

NCT05517226

/ Terminated临床1期

A Phase I, Parallel-group, Multi-center, Open-label, Investigation of the Pharmacokinetics, Safety and Tolerability of a Single Subcutaneous Injection of Cotadutide in Participants With Mild, Moderate or Severe Hepatic Impairment Compared to Participants With Normal Hepatic Function

This study will assess the pharmacokinetics (PK), safety, and tolerability of a single subcutaneous injection of cotadutide in participants with mild, moderate or severe hepatic impairment compared to participants with normal hepatic function.

开始日期2022-09-06

申办/合作机构

AstraZeneca PLC

[+1]

EUCTR2021-005484-53-AT

/ Not yet recruiting临床2期

A Phase II Randomized, Double-blind, Placebo-controlled, Proof-of-Concept Study to Evaluate the Safety and Efficacy of Cotadutide in Participants with Non-cirrhotic Non-alcoholic Steatohepatitis with Fibrosis - PROXYMO-ADVANCE

开始日期2022-07-28

申办/合作机构

AstraZeneca AB

100 项与 Cotadutide 相关的临床结果

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100 项与 Cotadutide 相关的转化医学

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100 项与 Cotadutide 相关的专利（医药）

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项与 Cotadutide 相关的文献（医药）

2025-01-01·European Journal of Clinical Investigation

Glucagon and glucagon‐like peptide‐1 dual agonist therapy: A possible future towards fatty kidney disease

Review

作者: Mallamaci, Francesca ; Ozbek, Lasin ; Guldan, Mustafa ; Copur, Sidar ; Zoccali, Carmine ; Kanbay, Mehmet

AbstractBackgroundObesity is a growing epidemic affecting approximately 40% of the adult population in developed countries with major health consequences and comorbidities, including diabetes mellitus and insulin resistance, metabolically associated fatty liver disease, atherosclerotic cardiovascular and cerebrovascular diseases and chronic kidney disease. Pharmacotherapies targeting significant weight reduction may have beneficial effects on such comorbidities, though such therapeutic options are highly limited. In this narrative review, we aim to evaluate current knowledge regarding dual agonist therapies and potential implications for managing fatty kidney and chronic kidney disease.Results and ConclusionGlucagon‐like peptide‐1 agonists and sodium‐glucose cotransporter‐2 inhibitors are two novel classes of glucose‐lowering medications with potential implications and beneficiary effects on renal outcomes, including estimated glomerular filtration rate, albuminuria and chronic kidney disease progression. Recently, dual agonist therapies targeting glucagon‐like peptide‐1 and glucagon receptors, namely survodutide and cotadutide, have been evaluated in managing metabolically associated fatty liver disease, a well‐established example of visceral obesity. Fatty kidney is another novel concept implicated in the pathophysiology of chronic kidney disease among patients with visceral obesity.

2024-12-01·Kidney International

A randomized phase 2b trial examined the effects of the glucagon-like peptide-1 and glucagon receptor agonist cotadutide on kidney outcomes in patients with diabetic kidney disease

Article

作者: Elliott, Tom G. ; Parkinson, Joanna ; Heerspink, Hiddo J L ; Elliott, Tom G ; Duck, Tabbatha ; Hansen, Lars ; Dumas, Richard ; Smith, Kirsten ; Derwahl, Karl-Michael ; Jolly, Simran ; Yu, Hongtao ; Peters, Carl ; Morales, Cristobal ; Heerspink, Hiddo J.L. ; Goldenberg, Ronald ; Lecube, Albert ; Parker, Victoria E R ; Jermutus, Lutz ; Selvarajah, Viknesh ; Robertson, Darren ; Scott, Russell ; Parker, Victoria E.R. ; Hess, Sonja ; Baker, John ; Khan, Anis ; Chung, H Sophia ; Chang, Yi-Ting ; Sánchez, José ; Coggi, Angela

Cotadutide is a glucagon-like peptide-1 (GLP-1) and glucagon receptor agonist that may improve kidney function in patients with type 2 diabetes (T2D) and chronic kidney disease (CKD). In this phase 2b study, patients with T2D and CKD (estimated glomerular filtration rate [eGFR] of 20 or more and under 90 mL/min per 1.73 m² and urinary albumin-to-creatinine ratio [UACR] over 50 mg/g) were randomized 1:1:1:1:1 to 26 weeks' treatment with standard of care plus subcutaneous cotadutide uptitrated to 100, 300, or 600 μg, or placebo daily (double-blind), or the GLP-1 agonist semaglutide 1 mg once weekly (open-label).The co-primary endpoints were absolute and percentage change versus placebo in UACR from baseline to the end of week 14. Among 248 randomized patients, mean age 67.1 years, 19% were female, mean eGFR was 55.3 mL/min per 1.73 m², geometric mean was UACR 205.5 mg/g (coefficient of variation 270.0), and 46.8% were receiving concomitant sodium-glucose co-transporter 2 inhibitors. Cotadutide dose-dependently reduced UACR from baseline to the end of week 14, reaching significance at 300 μg (-43.9% [95% confidence interval -54.7 to -30.6]) and 600 μg (-49.9% [-59.3 to -38.4]) versus placebo; with effects sustained at week 26. Serious adverse events were balanced across arms. Safety and tolerability of cotadutide 600 μg were comparable to semaglutide. Thus, our study shows that in patients with T2D and CKD, cotadutide significantly reduced UACR on top of standard of care with an acceptable tolerability profile, suggesting kidney protective benefits that need confirmation in a larger study.

2024-09-01·Clinical Gastroenterology and Hepatology

Safety and Efficacy of Novel Incretin Co-agonist Cotadutide in Biopsy-proven Noncirrhotic MASH With Fibrosis

Article

作者: Sanyal, Arun J ; Robertson, Darren ; Daniels, Samuel J ; Shankar, Sudha S ; Sarv, Janeli ; Jermutus, Lutz ; Carter, Debra ; Sánchez, José ; Challis, Benjamin

BACKGROUND & AIMSCotadutide, a peptide co-agonist at the glucagon-like peptide-1 (GLP-1) and glucagon (GCG) receptors, has demonstrated robust improvements in body weight, glycemia, and hepatic fat fraction (HFF) in patients living with obesity and type 2 diabetes mellitus.METHODSIn PROXYMO, a 19-week randomized double-blind placebo-controlled trial, the safety and efficacy of cotadutide (600 μg, 300 μg) or placebo were evaluated in 74 participants with biopsy-proven noncirrhotic metabolic dysfunction-associated steatohepatitis (MASH) with fibrosis. Analyses were performed using intent-to-treat and modified intent-to-treat population data.RESULTSDose- and time-dependent improvements in HFF, alanine aminotransferase (ALT), and aspartate aminotransferase (AST), markers of liver health, and metabolic parameters were observed with significant improvements after 19 weeks with 600 μg ([least squares] mean difference vs placebo, [95% confidence interval] for absolute HFF: -5.0% [-8.5 to -1.5]; ALT: -23.5 U/L [-47.1 to -1.8]; AST: -16.8 U/L [-33.0 to -0.8]). Incidences of any grade treatment-emergent adverse events (TEAEs) were 91.7%, 76.9%, and 37.5% with cotadutide 600 μg, 300 μg, and placebo, respectively. The majority were gastrointestinal, mild to moderate in severity, and generally consistent with other incretins at this stage of development. TEAEs leading to treatment discontinuation were 16.7%, 7.7%, and 4.2% with cotadutide 600 μg, 300 μg, and placebo, respectively.CONCLUSIONSPROXYMO provides preliminary evidence for the safety and efficacy of GLP-1/GCG receptor co-agonism in biopsy-proven noncirrhotic MASH with fibrosis, supporting further evaluation of this mechanism in MASH.CLINICAL TRIAL REGISTRATION NUMBERNCT04019561.

项与 Cotadutide 相关的新闻（医药）

2025-01-08

·国际糖尿病idiabetes

年终盘点 | 2024糖尿病肾脏病临床研究进展

点击“蓝字”关注我们年终盘点微专辑扫描二维码可查看更多内容糖尿病肾脏病（DKD）作为终末期肾病（ESRD）的首要病因，严重影响患者的生存质量，给全球带来沉重负担。聚焦2024年糖尿病肾脏病领域临床研究，精彩纷呈。本文中，天津医科大学朱宪彝纪念医院陈莉明教授盘点和梳理了2024年度JCR 1区发表的相关临床研究，以飨读者。 SGLT2/1双重抑制剂相关研究 01 索格列净与T2DM合并CKD患者肾脏结局、肾功能和白蛋白尿：SCORED研究的二次分析发表刊物Clin J Am Soc Nephol SCORED研究是一项多中心、随机对照临床试验，在10 584例2型糖尿病（T2DM）合并慢性肾脏病（CKD）患者中评估钠-葡萄糖共转运蛋白（SGLT）2/1双重抑制剂索格列净（Sotagliflozin）的心肾结局。本研究利用SCORED研究的估算肾小球滤过率（eGFR）数据进行探索性分析，以评价索格列净对预设肾脏复合终点及额外心肾复合终点的影响。依据实验室数据和病例报告表数据，识别出223个事件。结果显示，索格列净可降低eGFR持续下降>50%、eGFR<15 ml/min/1.73m2、透析或肾脏移植复合事件的风险，索格列净组和安慰剂组分别发生87个（1.6%）和136个（2.6%）事件（HR 0.62，95%CI：0.48~0.82，P<0.001）。同时，索格列净降低了心肾复合终点（定义为上述肾脏复合终点+心血管死亡或肾脏死亡）风险，索格列净组和安慰剂组分别发生239个（4.5%）和306个（5.7%）事件（HR 0.77，95%CI：0.65~0.91，P=0.0023）。SCORED研究的二次分析证实，索格列净可降低T2DM合并CKD患者肾脏和心肾复合终点的风险。图1. 肾脏复合终点累积发生率 GLP-1RA相关研究 02 司美格鲁肽对T2DM患者CKD的影响：FLOW研究发表刊物N Engl J Med T2DM合并CKD患者发生肾衰竭、心血管事件和死亡的风险很高，FLOW研究旨在评价胰高糖素样肽-1受体激动剂（GLP-1RA）司美格鲁肽1.0 mg每周一次皮下注射治疗在T2DM合并CKD患者中预防肾衰竭、肾功能严重受损以及肾性死亡或心血管死亡的疗效和安全性。本研究将T2DM合并CKD患者[eGFR 50~75 ml/min/1.73m2和尿白蛋白肌酐比值（UACR）>300~<5000 mg/g，或eGFR 25~<50 ml/min/1.73m2和UACR>100~<5000 mg/g]以1:1比例随机分配接受每周一次1.0 mg司美格鲁肽或安慰剂治疗。主要终点为首发肾脏复合事件（eGFR自基线持续降低≥50%、持续性eGFR<15 ml/min/1.73m2、起始长期肾脏替代治疗、肾脏相关或心血管原因死亡）。 3533例受试者中，中位随访3.4年。与安慰剂组相比，司美格鲁肽组的主要终点事件风险降低24%（HR 0.76，95%CI：0.66~0.88，P=0.0003），主要终点的肾脏特异性复合终点（HR 0.79，95%CI：0.66~0.94）和心血管原因死亡（HR 0.71，95%CI：0.56~0.89）的结果相似。司美格鲁肽组eGFR年均下降斜率较慢，为1.16 ml/min/1.73m2（P<0.001），主要心血管事件风险降低18%（HR 0.82，95%CI：0.68~0.98，P=0.029），全因死亡风险降低20%（HR 0.80，95%CI：0.67~0.95，P=0.01）。司美格鲁肽组报告严重不良事件的受试者比例低于安慰剂组（49.6% vs. 53.8%）。FLOW研究证实，司美格鲁肽治疗可降低T2DM合并CKD患者出现临床重要肾脏终点、主要心血管事件和全因死亡的风险。图2. 首发主要肾脏事件和首发肾脏特异性复合事件发生率 03 司美格鲁肽对T2DM患者DKD一级预防的影响：SUSTAIN 6随机对照试验的事后分析发表刊物Diabetes Obes Metab 众所周知，识别DKD高危人群并及时干预是预防DKD的关键。本研究采用已开发的DKD风险分类模型，评估司美格鲁肽或安慰剂对DKD一级预防的效果。受试者为SUSTAIN 6研究中基线无DKD的T2DM患者，接受0.5 mg或1.0 mg司美格鲁肽或安慰剂治疗，根据基线DKD风险进行分组，风险计算采用一个已验证的模型，主要事后分析结局是司美格鲁肽或安慰剂对发生DKD（UACR≥30 mg/g和/或eGFR<60 ml/min/1.73m²）患者比例的影响，其他事后分析结局包括随时间变化的DKD风险评分、UACR和eGFR的变化。结果显示，1139例受试者中，28.7%发展为DKD；更多的DKD高危受试者（952/1139）发展为DKD。与安慰剂相比，司美格鲁肽显著降低总体（OR 0.56，95%CI：0.42~0.74，P<0.0001）和DKD高危人群中发生DKD的风险（OR 0.51，95%CI：0.38~0.69，P<0.0001），显著延缓DKD进展，司美格鲁肽的有益作用主要由UACR变化驱动。本研究表明，司美格鲁肽可能对T2DM患者DKD的一级预防有益。图3. 治疗结束时，总体研究人群中DKD风险评分随时间的变化 GLP-1R/GCGR双重激动剂相关研究 04 GLP-1/GCG双受体激动剂对DKD患者肾脏结局的影响：一项2b期随机对照临床试验发表刊物Kidney Int Cotadutide是胰高糖素样肽-1受体（GLP-1R）和胰高糖素受体（GCGR）双重激动剂，可改善T2DM合并CKD患者的肾功能。在这项为期26周的2b期研究中，T2DM合并CKD患者（eGFR>20~<90 ml/min/1.73m2，UACR>50 mg/g）按照1:1:1:1:1比例随机分配至标准治疗加皮下注射Cotadutide分别100 μg、300 μg或600 μg，或安慰剂每日（双盲），或司美格鲁肽1 mg，每周一次（开放标签）。主要终点是UACR从基线到第14周结束的绝对变化以及与安慰剂相比的百分比变化。248例随机分组的T2DM患者平均年龄为67.1岁，平均eGFR为55.3 ml/min/1.73m2，UACR为205.5 mg/g，46.8%的患者同时接受SGLT2抑制剂治疗。从基线到第14周结束时，Cotadutide呈剂量依赖性地降低UACR，300 μg组（-43.9%，95%CI：-54.7 ~ -30.6）和600 μg组（-49.9%，95%CI：-59.3 ~ -38.4）的UACR下降相较安慰剂组的差异达到显著性；且效果持续至第26周。Cotadutide 600 μg组的安全性和耐受性与司美格鲁肽组相当。本研究表明，在T2DM合并CKD患者中，Cotadutide可显著降低UACR，具有可接受的耐受性。图4. 双受体激动剂Cotadutide治疗后UACR的改变联合用药相关研究 05 SGLT2i和GLP-1RA联合治疗对T2DM患者eGFR下降的影响：RECAP研究事后分析发表刊物Front pharmacol 在RECAP研究事后分析中，共纳入643例T2DM患者（GLP-1RA先导组，n=331；SGLT2i先导组，n=312），观察两组患者每年eGFR下降的差异。SGLT2i先导组中，联合GLP-1RA后，每年eGFR下降显著减少（先前：-3.5±9.4 ml/min/1.73m2/年，之后：-0.4±6.3 ml/min/1.73m2/年，P<0.001）；而GLP-1RA先导组，在开始SGLT2i后，eGFR下降趋势减缓，但未达统计学显著差异（先前：-2.0±10.9 ml/min/1.73m2/年，之后：-1.8±5.4 ml/min/1.73m2/年，P=0.83）。SGLT2i治疗患者加入GLP-1RA后，能够观察到每年eGFR下降减缓，由此可见SGLT2i和GLP-1RA联合治疗的肾脏益处，如每年eGFR下降，可能受到先前药物的影响。图5. SGLT2i先导组和GLP-1RA先导组联合治疗前后eGFR的变化 06 SGLT2i、GLP-1RA和ns-MRA联合治疗T2DM合并蛋白尿患者的终生心血管、肾脏和生存获益发表刊物Circulation SGLT2i、GLP-1RA以及非甾体类盐皮质激素受体拮抗剂（ns-MRA）非奈利酮均能单独减少T2DM合并蛋白尿患者的心血管、肾脏和死亡终点。然而，这些药物联合治疗的终生益处尚不清楚。本研究利用2项SGLT2i试验（CANVAS和CREDENCE）、2项ns-MRA试验（FIDELIO-DKD和FIGARO-DKD）以及8项GLP-1RA试验数据，以评估与常规治疗（肾素-血管紧张素系统阻断和传统风险因素控制）相比，三药联合治疗对心血管、肾脏和死亡结局的相对影响。作者采用精算方法，通过将估算的联合治疗效果应用于CANVAS和CREDENCE中接受常规治疗的受试者，在蛋白尿至少中度增加（UACR≥30 mg/g）的T2DM患者中评估联合SGLT2i、GLP-1RA和ns-MRA治疗的绝对风险降低。与传统治疗相比，SGLT2i、GLP-1RA和ns-MRA联合治疗的主要心血管不良事件（MACE，非致死性心肌梗死、非致死性卒中或心血管死亡）风险降低35%（HR 0.65，95%CI：0.55~0.76），相应的3年内估计绝对风险降低为4.4%（95%CI：3.0~5.7），需要治疗人数为23例（95%CI：18~33）。对于开始联合治疗的50岁患者，估计MACE无事件生存期为21.1年，而传统治疗组为17.9年（增加3.2年，95%CI：2.1~4.3）。预计的无心力衰竭住院（3.2年，95%CI：2.4~4.0）、无CKD进展（5.5年，95%CI：4.0~6.7）、无心血管死亡（2.2年，95%CI：1.2~3.0）和无全因死亡（2.4年，95%CI：1.4~3.4）的生存期均增加。因此，在蛋白尿至少中度增加的T2DM患者中，SGLT2i、GLP-1RA和ns-MRA联合治疗可能在无心肾事件生存期以及总体生存期方面带来益处。图6. 三药联合组与常规治疗组的无肾脏事件生存率 07 在FLOW试验中，司美格鲁肽联合或不联合SGLT2i对T2DM合并CKD受试者的影响发表刊物Nat Med 将FLOW试验中纳入的T2DM合并CKD患者根据基线SGLT2i使用情况（使用组n=550，未使用组n=2983）进行分层，并随机分至司美格鲁肽组或安慰剂组。主要终点为肾衰竭、eGFR降低≥50%、肾脏死亡或心血管死亡的复合终点。与安慰剂组相比，所有接受司美格鲁肽治疗的受试者主要终点风险降低24%（95%CI：34%~12%）。在基线使用SGLT2i的受试者中，司美格鲁肽组与安慰剂组的主要终点事件发生比例分别为41/277和38/273（HR 1.07，95%CI：0.69~1.67，P=0.755）；在基线未使用SGLT2i的受试者中，司美格鲁肽组与安慰剂组的主要终点发生比例分别为290/1490和372/1493（HR 0.73，95%CI：0.63~0.85，P<0.001；P交互作用=0.109）。在SGLT2i亚组和无SGLT2i亚组中，司美格鲁肽对总体eGFR斜率（ml/min/1.73m2/年）的治疗差异分别为0.75（95%CI：-0.01~1.5）和1.25（95%CI：0.91~1.58）（P交互作用=0.237）。可见，司美格鲁肽在减少肾脏终点方面的获益在基线使用或未使用SGLT2i的受试者中一致。图7. 司美格鲁肽联合与不联合SGLT2i对T2DM合并CKD患者的影响中药相关研究 08 T2DM合并CKD患者加用黄芪治疗：一项多中心、评估员盲法、随机对照试验发表刊物Phytomedicine 本研究为随机、评估者盲法、标准护理对照、多中心临床试验，旨在评价黄芪对大量蛋白尿的T2DM合并CKD患者肾功能下降的有效性。研究从香港7个公立门诊诊所和社区纳入118例eGFR 30~90 ml/min/1.73m2和UACR 300~5000 mg/g的患者，将其随机分至加用口服黄芪颗粒（相当于15 g/d生药）或继续标准治疗48周。主要终点是意向治疗人群的eGFR变化斜率和UACR。黄芪组的eGFR下降斜率估计差异为4.6 ml/min/1.73m2/年（95%CI：1.5~7.6，P=0.003），下降速度更慢。对于UACR，估计的组间变化斜率差异不显著（1.14，95%CI：0.85~1.52，P=0.392）。31例黄芪治疗患者和41例标准治疗患者发生不良事件。黄芪治疗组患者第48周末收缩压降低7.9 mmHg（95%CI：-12.9 ~ -2.8，P=0.003）。这提示，T2DM合并CKD患者加用黄芪治疗，在标准治疗的基础上能够进一步稳定肾功能。图8. 加用黄芪组和标准治疗组的eGFR和UACR改变参考文献（上下滑动可查看） 1. Sridhar VS, et al. Sotagliflozin and Kidney Outcomes, Kidney Function, and Albuminuria in Type 2 Diabetes and CKD: A Secondary Analysis of the SCORED Trial. Clin J Am Soc Nephrol. 2024；19(5): 557-564. DOI: 10.2215/cjn.0000000000000414. 2. Perkovic V, et al. Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes. N Engl J Med. 2024; 391(2): 109-121. DOI: 10.1056/NEJMoa2403347. 3. Wang J, et al. Effect of semaglutide on primary prevention of diabetic kidney disease in people with type 2 diabetes: A post hoc analysis of the SUSTAIN 6 randomized controlled trial. Diabetes Obes Metab. 2024; 26(11): 5157-5166. DOI: 10.1111/dom.15860. 4. Selvarajah V, et al. A randomized phase 2b trial examined the effects of the glucagon-like peptide-1 and glucagon receptor agonist cotadutide on kidney outcomes in patients with diabetic kidney disease. Kidney Int. 2024; 106(6): 1170-1180. DOI: 10.1016/j.kint.2024.08.023. 5. Muta Y, et al. Influence of the combination of SGLT2 inhibitors and GLP-1 receptor agonists on eGFR decline in type 2 diabetes: post-hoc analysis of RECAP study. Front Pharmacol. 2024; 15: 1358573. DOI: 10.3389/fphar.2024.1358573. 6. Neuen BL, et al. Estimated Lifetime Cardiovascular, Kidney, and Mortality Benefits of Combination Treatment With SGLT2 Inhibitors, GLP-1 Receptor Agonists, and Nonsteroidal MRA Compared With Conventional Care in Patients With Type 2 Diabetes and Albuminuria. Circulation. 2024; 149(6): 450-462. DOI: 10.1161/circulationaha.123.067584. 7. Mann JFE, et al. Effects of semaglutide with and without concomitant SGLT2 inhibitor use in participants with type 2 diabetes and chronic kidney disease in the FLOW trial. Nat Med. 2024; 30(10): 2849-2856. DOI: 10.1038/s41591-024-03133-0. 8. Chan KW, et al. Add-on astragalus in type 2 diabetes and chronic kidney disease: A multi-center, assessor-blind, randomized controlled trial. Phytomedicine. 2024; 130: 155457. DOI: 10.1016/j.phymed.2024.155457. 声明：本文仅供医疗卫生专业人士了解最新医药资讯参考使用，不代表本平台观点。该等信息不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议，如果该信息被用于资讯以外的目的，本站及作者不承担相关责任。最新《国际糖尿病》读者专属微信交流群建好了，快快加入吧！扫描左边《国际糖尿病》小助手二维码（微信号：guojitnb），回复“国际糖尿病读者”，ta会尽快拉您入群滴！（来源：《国际糖尿病》编辑部）版权声明版权属《国际糖尿病》所有。欢迎个人转发分享。其他任何媒体、网站未经授权，禁止转载。

临床结果临床研究临床终止

2024-10-28

·药智网

2024年集体爆发的MASH市场，竞争格局几何？

继今年3月，全球首款MASH新药——Resmetirom获FDA批准用于治疗伴有肝纤维化的成人MASH患者，填补了MASH药物的空白状态后，近段时间以来，国内MASH领域的“新药曝光度”有目共睹的在增加。 10月15日，微芯生物宣布，其研发的西格列他钠治疗非酒精性脂肪性肝炎（NASH）/代谢相关性脂肪性肝炎（MASH）的2期临床研究（CGZ203试验）摘要入选美国肝病研究学会年会（AASLD 2024），11月17日以口头报告形式公布。 10月18日，中国国家药监局药品审评中心（CDE）官网公示，康弘药业1类THR-β新药KH629片获得临床试验默示许可，拟开发用于治疗成人非酒精性脂肪性肝炎。为何沉寂40余年的MASH新药研究，短时间内俨然成为“流量”的代名词，成为众多药企争相入局的潜力市场，其背后又是怎样的底层逻辑使然？患病率高涨 MASH是临床需求愈发迫切其实，与大多数肝脏慢性病不同，近年来非酒精性脂肪性肝病（NAFLD）的患病率不降反增，现阶段已取代乙肝成为我国最常见的慢性肝病。资料显示，中国成年人中NAFLD患病率高达29.2%，10年内整体增长10%，中国MASH患病率约为2.4%～6.1%，我国NAFLD/MASH患者疾病负担极其沉重。据弗若斯特沙利文报告预计， 2030 年全球 MASH 患病人数将达到 4.9 亿人，全球MASH药物市场将达到 322 亿美元。作为NAFLD中最严重的发展阶段，原理上MASH是一种与代谢紊乱相关的肝脏疾病，其特征是肝脏中脂肪的异常积累，伴随着炎症和肝细胞损伤，早年间被称为非酒精性脂肪性肝炎（NASH）。 40余年的相关研究下，人们对MASH的发病机制仍尚未完全明确，目前认为其乃是一种代谢应激性肝损伤，与多种因素相关，复杂的级联反应下的肝细胞损伤机制有以下几种，主要包括胰岛素抵抗、氧化应激、炎症反应和脂质代谢异常等多个环节。在临床表现方面，MASH通常情况下起病隐匿且缓慢，且通常无症状，多于常规检查过程中无意发现，并且由于MASH通常情况下难以自发缓解，在早期无干预的情况下进展为肝纤维化的风险很高，大约有15%的患者会发展为肝硬化、肝衰竭和肝细胞癌。临床药物缺乏 MASH传统治疗局限性大在Resmetirom获FDA批准上市之前，全球尚无治疗 NAFLD/NASH 的靶向性药物，而由于MASH与肥胖、2 型糖尿病、高血压、血脂紊乱等疾病的密切相关性，目前普遍认为控制这些疾病可有效改善 NAFLD/NASH的代谢状态，从而延缓疾病进展。因此，NAFLD以及MASH的治疗基础仍是生活方式的干预和饮食方案的优化，生活习惯的改善，尤其饮食的控制及锻炼减重等可减少肝脏脂肪沉积，有利于改善 MASH 的生化指标和肝组织学病变，相关研究显示，体重减轻 3% 即可改善 NAFLD患者脂肪肝病情程度，减重 7% 可改善肝脏炎症等组织学指标，减重 10% 可逆转肝纤维化水平。而在药物治疗方面，临床上主要针对抗胰岛素抵抗、抗氧化应激、降血脂、促进脂质代谢及保护肝细胞膜等对MASH进行治疗，如二甲双胍、维生素 E、熊去氧胆酸、FXR激动剂奥贝胆酸、肝损伤治疗药物等保肝药物的使用。但同时，上述药物治疗方式的局限性也很大，一者药物的治疗剂量、有效性及安全性均尚不明确，有待进一步研究；二者，如奥贝胆酸等FXR激动剂的不良反应也极大限制了其在MASH领域的应用。故现阶段的MASH临床治疗上，迫切需要一种副作用低、能逆转肝纤维化、患者顺应性佳的创新疗法。四大方向推动MASH机制逐渐清晰就目前而言，通过对MASH的发病机制研究，目前已有多款靶点给予了MASH有效干预，是目前乃至未来MASH治疗的主要方向。从类型上来看主要分为代谢、消化、抗炎、抗纤维化四种方向：代谢类：改善胰岛素敏感性、抑制脂肪生成各种酶、促进线粒体摄取脂肪酸等。消化类：调控肝肠轴的循环、改善胆汁酸的循环与信号传导、改善肠道菌群的平衡等。抗炎类：抑制炎症细胞聚集、阻断炎性信号传导、降低氧化作用和内质网应激反应、防止肝细胞凋亡等。抗纤维化：针对肝脏中的星形细胞、减轻肝脏中胶原蛋白的沉积、增强纤维分解等。而在这四种类型药物之下，又可以细分出不同的靶点选择，各靶点方向之下又存在不同的技术优势与产品差异。数据来源：公开数据整理（点击查看大图）据不完全统计，全球现有MASH在研疗法已突破350款。其中代谢类与消化类的数量最多，而前者主要机制集中于肝内，在逆转纤维化方面具有优势，而后者则是从肝外机制着手，在降低肝脏脂肪积累与纤维化进展方面优势明显，两者机制各有优劣，未来大概率会是协同合作的关系。临床阶段方面，虽绝大多数创新疗法均集中在临床前阶段，但跨入临床阶段的产品依旧不少，其中以临床II期管线数量最多，共计108款；而进入临床III期产品则也有18款之多。表1.MASH临床III期管线药品名称靶点适应症最高阶段原研单位利莫纳班 rimonabant CB1 临床Ⅲ期赛诺菲依碳酸瑞格列净 remogliflozin etabonate SLC5A2 临床Ⅲ期 BHV Pharma Inc;格兰马克制药有限公司沙格列扎镁 aroglitazar magnesium INS 临床Ⅲ期 Zydus Lifesciences Ltd 司美格鲁肽 semaglutide GLP-1R 临床Ⅲ期丹麦诺和诺德公司腺苷蛋氨酸 ademetionine Transferase 临床Ⅲ期雅培制药芦比前列酮 lubiprostone CFTR;ClC-2;PGE1 临床Ⅲ期 Sucampo Pharma LLC 佩玛贝特 pemafibrate PPAR-alpha 临床Ⅲ期 Kowa Co Ltd 塞拉德帕 seladelpar PPAR-delta 临床Ⅲ期 CymaBay Therapeutics Inc;强生创新制药 aramchol SCD1 临床Ⅲ期 Galmed Pharmaceuticals Ltd survodutide GLP-1R;GCGR 临床Ⅲ期 Zealand Pharma A/S;勃林格殷格翰 FXR314 NR1H4 临床Ⅲ期 Organovo Holdings inc 拉尼兰诺 lanifibranor PPAR-alpha;PPAR-delta;PPAR-gamma 临床Ⅲ期 Inventiva 可妥度肽 cotadutide GLP-1;GCGR 临床Ⅲ期阿斯利康瑟隆舍替selonsertib MAP3K5 临床Ⅲ期美国吉利德科学公司塞尼韦洛 cenicriviroc CCR2;CCR5 临床Ⅲ期 Tobira Therapeutics Inc;武田药品工业株式会社 ENB-106 / 临床Ⅲ期上海轶诺药业有限公司依鲁西夫明 efruxifermin FGF21 临床Ⅲ期安进公司 norucholic acid / 临床Ⅲ期德国霍克大药厂数据来源：药智数据三大靶点引领MASH新药加速落地就MASH在研药物靶点分布上而言，glp-1、FXR、THR-β、FGF19/21与PPAR是现阶段MASH最主要的在研药物类型。数据来源：药智数据从数量上来看，FXR激动剂、GLP1在研发热度上远超其他靶点，其在研数量也最多，目前均有超过30款相关疗法布局；其次是THR-β、FGF19/21与PPAR，分别有19、18与13款新药布局；其余靶点数量则相对较少，其临床阶段也相对靠后。从趋势上来看，FXR激动剂虽然是MASH领域的老牌靶点之一，但由于靶点特殊作用机制，其在副作用上的局限性太大，直接影响了其在临床上的应用潜力。至少就现在而言，反而是glp-1与THR-β两种机制的MASH新药更受关注，未来也更容易占据头牌。数据来源：药智数据 GLP-1 由于原理上GLP-1类似物能够有效改善糖脂代谢异常，因此GLP-1受体激动剂在糖尿病与减重适应症外，也被视为潜在的MASH治疗药物。表2.GLP-1应用于MASH的创新疗法药品名称靶点原研单位适应症最高阶段司美格鲁肽 semaglutide GLP-1R 丹麦诺和诺德公司临床Ⅲ期 survodutide GLP-1R;GCGR Zealand Pharma A/S;勃林格殷格翰临床Ⅲ期可妥度肽 cotadutide GLP-1;GCGR 阿斯利康临床Ⅲ期替尔泊肽 tirzepatide GIPR;GLP-1R 礼来制药临床Ⅱ期 RAY-1225 GLP-1;GIP 广东众生睿创生物科技有限公司临床Ⅱ期 HEC-88473 FGF21;GLP-1R 东莞市东阳光生物药研发有限公司临床Ⅱ期派维度肽 pemvidutide GLP-1R;GCGR Altor BioScience Corp合作：Altimmune Inc 临床Ⅱ期尤曲格鲁肽 utreglutide GLP-1R 印度太阳药业有限公司临床Ⅱ期巴度肽 bamadutide GLP-1R;GCGR 赛诺菲临床Ⅱ期依福培肽 efocipegtrutide GIPR;GLP-1R;GCGR 韩美药品株式会社临床Ⅱ期数据来源：药智数据截止目前，随着人们对 GLP-1 的焦点由减肥向在抗 MASH转变之下，已有超30种GLP-1药物正在研究其治疗MASH的潜力，临床上推进较快的产品不少，较出名的产品有诺和诺德的司美格鲁肽、勃林格殷格翰的survodutide、阿斯利康的cotadutide、礼来制药的tirzepatide。其中，Semaglutide与替尔泊肽作为GLP-1两大重磅产品，在关于MASH的治疗研究中均显示出减少肝脏脂肪积累、降低炎症水平的潜力，极大地振奋了行业对GLP-1作用于MASH的信心。但与此同时，GLP-1在治疗MASH上的局限性也逐渐体现，即虽然在减少肝脏脂肪积累和纤维化方面的效果显著，但对逆转肝脏纤维化上却缺乏足够、全面、多维度的有效证据。这就导致GLP-1疗法单药治疗既无法完全满足现有的临床需求，也很难与其他疗法拉开差距。对此，有关人士表示，GLP-1未来要想在MASH领域站稳脚跟，要么就逆转纤维化做出更多差异化成果，要么依靠肝外机制改善代谢紊乱的特点，与众多肝内机制的MASH疗法形成联动与互补，以协同策略解决MASH的临床需求。 Fxr（NR1H4）作为曾经治疗MASH最重要的靶点，也是MASH早期阶段最主要的在研药物形式，FXR作为一种肠肝调节因子，不仅参与胆汁酸信号传导，调控胆汁酸合成和转运，还可以调节葡萄糖稳态、脂质和胆固醇代谢等其他生理功能以及抑制炎症，在MASH治疗上，目前已显示出一定的治疗效果。截止目前，除已经宣布终止MASH适应症开发的奥贝胆酸外，领域内仍有超过30款Fxr激动剂涉及MASH适应症，其中Organovo的FXR314已进入了临床III期，是现阶段推进最快的Fxr激动剂；之后，还有10余款管线进入了临床II期，较受期待的有吉利德的cilofexor、诺华制药的nidufexor、东阳光药业HEC96719等。表3.MASH中Fxr激动剂创新疗法药品名称靶点原研单位适应症最高阶段奥贝胆酸 obeticholic acid NR1H4 Intercept Pharmaceuticals Inc 注册申请 FXR314 NR1H4 Organovo Holdings inc 临床Ⅲ期昔洛法克索 cilofexor NR1H4 Phenex Pharmaceuticals AG;美国吉利德科学公司临床Ⅱ期尼度法克索 nidufexor NR1H4 诺华制药临床Ⅱ期 HEC96719 NR1H4 广东东阳光药业股份有限公司临床Ⅱ期卓匹非索 tropifexor NR1H4 诺华制药临床Ⅱ期 CS-0159 NR1H4 Van Andel Institute;中国科学院上海药物研究所;凯思凯迪（上海）医药科技有限公司临床Ⅱ期 EDP-305 NR1H4 Enanta Pharmaceuticals Inc 临床Ⅱ期 TERN-101 NR1H4 上海拓臻生物科技有限公司;礼来制药临床Ⅱ期 MET-642 NR1H4 Metacrine Inc 临床Ⅱ期 MET-409 NR1H4 Metacrine Inc 临床Ⅱ期 HPG1860 NR1H4 雅创医药技术（上海）有限公司临床Ⅱ期 EYP-001 NR1H4 Poxel SA 临床Ⅱ期数据来源：药智数据而与此同时，虽然近年来Fxr激动剂领域用于MASH治疗的研究开发正在进入快速发展期，但临床获益有限，副作用严重等局限性也制约了其在临床上应用，最显著的例子就是奥贝胆酸，其2015年获FDA突破性疗法资格认定，是全球第一个进入临床3期的MASH候选产品，但最终仍因获益不确定性、副作用较大而折戟，经历多次被FDA否决后，最终无奈宣布终止其用于MASH领域的开发。因此，对于Fxr激动剂整体而言，在保证创新疗法的有效性，研究机构未来更大的精力或将集中于创新疗法的不良反应的减少与安全性的提高上。 THR-β THR-β是一种核激素受体，其主要在肝脏中高表达，能够调节脂代谢，降低低密度脂蛋白胆固醇（LDL-C）、甘油三酯和致动脉粥样硬化性脂蛋白，因此成为理论上MASH最具潜力的治疗靶点。此外，THR-β还可以通过促进脂肪酸的分解和刺激线粒体的生物发生来减少脂肪毒性并改善肝功能，进而减少肝脏脂肪。这也是为何THR-β激动剂会具备调控多种肝脏代谢通路来治疗MASH的潜力的原因。其在MASH上的主要作用有以下5点：调控脂肪合成调控脂肪酸氧化作用调控胆固醇代谢调控线粒体功能通过抑制TGF-β信号通路发挥抗炎和抗纤维化作用 2024年3月，Resmetirom成为首款获FDA批准上市的治疗代谢功能障碍相关脂肪性肝炎（MASH）的新药，也是THR-β激动剂领域首款撞线的产品。表4.MASH中THR-β激动剂创新疗法药品名称靶点原研单位适应症最高阶段瑞司美替罗 resmetirom THRB Madrigal Pharmaceuticals Inc;罗氏制药批准上市 VK-2809 THRB Ligand Pharmaceuticals Inc;Viking Therapeutics Inc 临床Ⅱ期 ASC41 THRB 歌礼制药有限公司;甘莱制药有限公司临床Ⅱ期 TERN-501 THRB 上海拓臻生物科技有限公司临床Ⅱ期 HSK-31679 THRB 海思科医药集团股份有限公司临床Ⅱ期 ALG-055009 THRB Aligos Therapeutics Inc 临床Ⅰ期 ASC-43-F THRB;NR1H4 歌礼制药有限公司;甘莱制药有限公司临床Ⅰ期 RJ-4287 THRB 南京奥利墨斯医药科技有限公司临床Ⅰ期 Kylo-0603 THRB 厦门甘宝利生物医药有限公司临床Ⅰ期 CS-060304 THRB 凯思凯迪（上海）医药科技有限公司临床Ⅰ期 CS-060380 THRB 凯思凯迪（上海）医药科技有限公司临床Ⅰ期数据来源：药智数据 Resmetirom的成功获批一方面为MASH患者的治疗提供了新手段，同时另一方面也证明了THR-β激动剂路线的可行性。也正是因此，THR-β激动剂成为全球MASH新药研发的主要集中方向，多款THR-β激动剂紧随其后，均表现出不俗的潜力，目前临床阶段进展较快的主要有四款，分别是Ligand的VK-2809、歌礼制药的ASC41、拓臻生物的TERN-501以及海思科的HSK-31679，均已进入了临床II期。而更值得注意的是，THR-β激动剂也是目前国内MASH在研新药最集中的方向，处于领先地位（临床进度靠前）的创新疗法数量远高于其他几种类型。未来，不出意外的话，国内在该领域的突破大概率也将集中此，或许还有望领先于海外药企，成为MNC争夺的关键。小结纵观MASH领域40余年的发展历史，从致病机制的不断完善，到临床上的对症治疗出现，再到今年首款新药获批上市，MASH的新药研发充满坎坷。但随着MASH新药研发的四大机制方向、10余款创新靶点的逐步落地，领域内似乎正在逐渐形成一个系统化、宏观化的研发格局，过程中不断有更多如GLP-1、THR-β等全新的疗法加入，至少目前看来俨然一副百废待兴，可大展拳脚的状态。而对于国内药企而言，虽然某种程度上做不到如海外一般全赛道布局，但在个别如THR-β激动剂等潜力领域的优势却反而更大，或许这种强调聚焦的国内赛道模式，未来或许真能让中国企业站上国际舞台，成为MASH领域的龙头之一。来源 | 博药（药智网获取授权转载）撰稿 | 头孢责任编辑 | 八角声明：本文系药智网转载内容，图片、文字版权归原作者所有，转载目的在于传递更多信息，并不代表本平台观点。如涉及作品内容、版权和其它问题，请在本平台留言，我们将在第一时间删除。商务合作 | 王存星 19922864877（同微信）阅读原文，是受欢迎的文章哦

ASH会议临床2期申请上市临床结果上市批准

2024-09-30

·PRNewswire

NeuroBo Pharmaceuticals Announces Positive Top-Line Data From the SAD Part 1 of Its Phase 1 Clinical Trial Evaluating DA-1726 for the Treatment of Obesity

Data Revealed Favorable Safety, Tolerability and Dose-Linear Pharmacokinetics (PK) Top-Line Data Readout from the MAD Part 2 Expected in the First Quarter of 2025 Planned Phase 1 Part 3 Will Evaluate Early Proof of Concept CAMBRIDGE, Mass., Sept. 30, 2024 /PRNewswire/ -- NeuroBo Pharmaceuticals, Inc. (Nasdaq: NRBO), a clinical-stage biotechnology company focused on transforming cardiometabolic diseases, today announced positive top-line safety, tolerability, and dose-linear pharmacokinetics (PK) data from the single ascending dose (SAD) Part 1 of its Phase 1 clinical trial of DA-1726, a novel, dual oxyntomodulin (OXM) analog agonist that functions as a glucagon-like peptide-1 receptor (GLP1R) and glucagon receptor (GCGR), for the treatment of obesity. In the SAD Part 1 of the Phase 1 clinical trial, a total of 45 obese, otherwise healthy participants were randomized in a double-blind, 6:3 ratio of DA-1726 or placebo. Single ascending doses were found to be safe and well tolerated, with no serious adverse events. Only 5 subjects in the DA-1726 treatment group reported adverse events (AEs) compared with 3 subjects in the placebo group. A dose-linear PK profile was observed across the investigated dose range. Additional cohorts are being added to the SAD Part 1 to explore the maximum tolerated dose. "The safety, tolerability and dose-linear PK data generated from the Part 1 SAD trial are highly encouraging and allowed for the accelerated initiation of our multiple ascending dose (MAD) study," stated Hyung Heon Kim, President and Chief Executive Officer of NeuroBo. "In light of the strong safety profile from the SAD Part 1 of the study, we are in the process of adding one or more cohorts to further explore the maximum tolerated dose, which will allow us to realize the full potential of DA-1726. Based on the preclinical data generated to date, as well as DA-1726's balanced activation of GLP1R and glucagon receptors, which increases energy expenditure, we continue to believe that DA-1726 may become a best-in-class obesity drug with a better tolerability profile than currently marketed GLP-1 agonists, and those now in late-stage clinical trials. We eagerly anticipate reporting top-line data from the MAD Part 2 in the first quarter of 2025, which will give us an early read on clinical efficacy. Additionally, we continue to plan Part 3 of the trial that will explore early proof of concept." The MAD Part 2 of the Phase 1 trial is a randomized, placebo-controlled, double-blind study to investigate the safety, tolerability, PK, and PD of multiple ascending doses of DA-1726 in obese, otherwise healthy subjects. Part 2 is expected to enroll approximately 36 participants, who will be randomized at the same 6:3 ratio into 4 planned cohorts, each to receive 4 weekly administrations of DA-1726 or placebo. The first patient in the MAD study was dosed ahead of schedule, in late June, as previously reported. The primary endpoint of the Phase 1 trial is to assess the safety and tolerability of DA-1726 by monitoring adverse events (AEs), serious adverse events (SAEs), treatment emergent adverse events (TEAEs) and AEs leading to treatment discontinuation. Secondary endpoints include the PK of DA-1726, assessed via serum concentrations over time and metabolite profiling at the highest doses of DA-1726. Exploratory endpoints will include the effect of DA-1726 on metabolic parameters, cardiac parameters, fasting lipid levels, body weight, waist circumference and body mass index (BMI), among others. For more information on this clinical trial, please visit: NCT06252220. About DA-1726 DA-1726 is a novel oxyntomodulin (OXM) analogue functioning as a GLP1R/GCGR dual agonist for the treatment of obesity and Metabolic Dysfunction-Associated Steatohepatitis (MASH) that is to be administered once weekly subcutaneously. DA-1726 acts as a dual agonist of GLP-1 receptors (GLP1R) and glucagon receptors (GCGR), leading to weight loss through reduced appetite and increased energy expenditure. DA-1726 has a well understood mechanism and, in pre-clinical mice models, resulted in improved weight loss compared to semaglutide (Wegovy®) and cotadutide (another OXM analogue). Additionally, in pre-clinical mouse models, DA-1726 elicited similar weight reduction, while consuming more food, compared tirzepatide (Zepbound®) and survodutide (a drug with the same MOA), while also preserving lean body mass and demonstrating improved lipid-lowering effects compared to survodutide. About NeuroBo Pharmaceuticals NeuroBo Pharmaceuticals, Inc. is a clinical-stage biotechnology company focused on transforming cardiometabolic diseases. The company is currently developing DA-1726 for the treatment of obesity, and is developing DA-1241 for the treatment of Metabolic Dysfunction-Associated Steatohepatitis (MASH). DA-1726 is a novel oxyntomodulin (OXM) analogue that functions as a glucagon-like peptide-1 receptor (GLP1R) and glucagon receptor (GCGR) dual agonist. OXM is a naturally-occurring gut hormone that activates GLP1R and GCGR, thereby decreasing food intake while increasing energy expenditure, thus potentially resulting in superior body weight loss compared to selective GLP1R agonists. DA-1241 is a novel G-protein-coupled receptor 119 (GPR119) agonist that promotes the release of key gut peptides GLP-1, GIP, and PYY. In pre-clinical studies, DA-1241 demonstrated a positive effect on liver inflammation, lipid metabolism, weight loss, and glucose metabolism, reducing hepatic steatosis, hepatic inflammation, and liver fibrosis, while also improving glucose control. For more information, please visit . Forward Looking Statements Certain statements in this press release may be considered forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as "believes", "expects", "anticipates", "may", "will", "should", "seeks", "approximately", "potential", "intends", "projects", "plans", "estimates" or the negative of these words or other comparable terminology (as well as other words or expressions referencing future events, conditions or circumstances) are intended to identify forward-looking statements. Forward-looking statements are predictions, projections and other statements about future events that are based on current expectations and assumptions and, as a result, are subject to risks and uncertainties. Many factors could cause actual future events to differ materially from the forward-looking statements in this press release, including, without limitation, those risks associated with NeuroBo's ability to execute on its commercial strategy; the timeline for regulatory submissions; the ability to obtain regulatory approval through the development steps of NeuroBo's current and future product candidates; the ability to realize the benefits of the license agreement with Dong-A ST Co. Ltd., including the impact on future financial and operating results of NeuroBo; the cooperation of NeuroBo's contract manufacturers, clinical study partners and others involved in the development of NeuroBo's current and future product candidates; potential negative interactions between NeuroBo's product candidates and any other products with which they are combined for treatment; NeuroBo's ability to initiate and complete clinical trials on a timely basis; NeuroBo's ability to recruit subjects for its clinical trials; whether NeuroBo receives results from NeuroBo's clinical trials that are consistent with the results of pre-clinical and previous clinical trials; impact of costs related to the license agreement, known and unknown, including costs of any litigation or regulatory actions relating to the license agreement; the effects of changes in applicable laws or regulations; the effects of changes to NeuroBo's stock price on the terms of the license agreement and any future fundraising; and other risks and uncertainties described in NeuroBo's filings with the Securities and Exchange Commission, including NeuroBo's most recent Annual Report on Form 10-K. Forward-looking statements speak only as of the date when made. NeuroBo does not assume any obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law. Contacts: NeuroBo Pharmaceuticals Marshall H. Woodworth Chief Financial Officer +1-857-299-1033 [email protected] Rx Communications Group Michael Miller +1-917-633-6086 [email protected] SOURCE NeuroBo Pharmaceuticals, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

临床1期临床结果引进/卖出

100 项与 Cotadutide 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D11304	Cotadutide	-	DB15194

研发状态

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
非酒精性脂肪性肝炎	临床前	瑞士	AstraZeneca AB	2022-07-12
非酒精性脂肪性肝炎	临床前	新加坡	阿斯利康全球研发（中国）有限公司	2022-07-12
非酒精性脂肪性肝炎	药物发现	澳大利亚	阿斯利康全球研发（中国）有限公司	2022-07-12
非酒精性脂肪性肝炎	药物发现	澳大利亚	AstraZeneca AB	2022-07-12
非酒精性脂肪性肝炎	药物发现	以色列	阿斯利康全球研发（中国）有限公司	2022-07-12
非酒精性脂肪性肝炎	药物发现	瑞士	AstraZeneca AB	2022-07-12
非酒精性脂肪性肝炎	药物发现	新加坡	阿斯利康全球研发（中国）有限公司	2022-07-12
非酒精性脂肪性肝炎	药物发现	澳大利亚	AstraZeneca AB	2022-07-12
非酒精性脂肪性肝炎	药物发现	以色列	阿斯利康全球研发（中国）有限公司	2022-07-12
非酒精性脂肪性肝炎	药物发现	澳大利亚	阿斯利康全球研发（中国）有限公司	2022-07-12

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临床结果

适应症

分期

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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


NCT03555994 (CTgov)	临床2期	2型糖尿病 \| 肥胖	51	Placebo (Placebo (Part A))	構獵顧淵顧選衊醖憲積(廠齋觸壓鬱壓觸顧膚構) = 餘鹽蓋顧範壓蓋壓窪壓遞餘襯製齋願憲襯觸壓 (鑰製遞願蓋憲襯壓鹹鏇, 廠簾網遞簾構蓋窪簾積 ~ 繭網鑰艱獵鹹鹽糧繭獵) 更多	-	2024-11-12
				MEDI0382 (MEDI0382 (Part A))	構獵顧淵顧選衊醖憲積(廠齋觸壓鬱壓觸顧膚構) = 壓遞範醖餘鏇憲願遞鹽遞餘襯製齋願憲襯觸壓 (鑰製遞願蓋憲襯壓鹹鏇, 簾築鏇膚壓製襯蓋憲糧 ~ 構窪夢顧選顧淵構夢製) 更多
NCT04019561 (PROXYMO, Pubmed) 人工标引	临床2期	非酒精性脂肪性肝炎 \| 代谢功能障碍相关的脂肪肝病	74	Cotadutide 600 μg	(網網淵壓製構積範餘積) = 夢壓鹽構醖鬱鹹齋選窪積遞壓獵獵構餘壓願齋 (簾糧構顧範獵艱膚選齋 ) 更多	积极	2024-05-09
				Cotadutide 300 μg	(襯築夢艱鹽齋願觸願淵) = 窪廠繭鑰廠構糧鑰願觸鑰醖構蓋蓋築顧顧夢夢 (蓋鹽糧膚構簾築範構艱 ) 更多
ADA2023	N/A	-	-	DA-1726	(鹹夢鑰窪蓋廠獵簾製願) = 網鏇淵餘鏇襯願齋築蓋願壓鑰遞選壓艱鏇壓襯 (積鹹淵淵艱糧襯遞壓蓋 ) 更多	-	2023-06-20
				Cotadutide	(鹹夢鑰窪蓋廠獵簾製願) = 憲衊選夢齋艱糧網選壓願壓鑰遞選壓艱鏇壓襯 (積鹹淵淵艱糧襯遞壓蓋 )
NAASO2022	临床2期	肥胖	18	Cotadutide	(餘壓廠鏇艱窪廠繭衊襯) = 繭淵憲製鬱鹹窪窪鏇糧鹹範選襯簾選簾齋願襯 (範衊顧憲憲構遞遞鬱鏇 ) 更多	-	2022-11-21
				Placebo	(餘壓廠鏇艱窪廠繭衊襯) = 艱鹹壓簾糧遞鏇廠壓鹽鹹範選襯簾選簾齋願襯 (範衊顧憲憲構遞遞鬱鏇 ) 更多
NCT03550378 (Pubmed) 人工标引	临床2期	2型糖尿病 \| 慢性肾病	41	Cotadutide	鏇糧選蓋鑰構淵觸衊窪(獵觸衊鏇淵積憲齋鏇獵) = 鹹膚艱齋衊鏇淵鏇窪蓋築壓獵鑰範鬱窪構衊顧 (網淵夢醖壓範淵鹽鹹獵 ) 更多	积极	2022-04-11
				Placebo	鏇糧選蓋鑰構淵觸衊窪(獵觸衊鏇淵積憲齋鏇獵) = 遞構網醖壓齋網窪製製築壓獵鑰範鬱窪構衊顧 (網淵夢醖壓範淵鹽鹹獵 ) 更多
NCT03444584 (EASD2021)	临床2期	2型糖尿病 \| 超重追加	49	Cotadutide+Dapagliflozin+Metformin	壓襯醖齋襯願廠廠鏇襯(築壓艱蓋構艱餘觸鑰築) = 醖範窪獵獵鏇夢鹽積積構構鏇觸糧鹹襯鏇鹹鹽 (窪製襯窪願壓鏇壓艱觸 ) 更多	积极	2021-09-30
NCT03645421 (Pubmed) 人工标引	临床1/2期	2型糖尿病 \| 超重 \| 肥胖	61	cotadutide	(獵觸獵齋顧壓膚簾範範) = no serious adverse events. 艱壓築餘繭網範鑰夢範 (餘壓衊選築醖壓夢餘淵 ) 更多	积极	2021-08-01
				Placebo
ADA2021	N/A	2型糖尿病肥胖	-	Cotadutide	(鏇觸繭衊觸構餘鹹遞製) = 鬱獵製糧衊簾鹽衊膚衊獵築淵繭鏇艱鹽鑰鏇鏇 (窪願獵窪蓋淵憲夢範積, -4.85%, ~ 3.10%) 更多	-	2021-06-01
				Placebo	(鏇觸繭衊觸構餘鹹遞製) = 餘糧壓鏇淵淵餘願膚餘獵築淵繭鏇艱鹽鑰鏇鏇 (窪願獵窪蓋淵憲夢範積, -2.66%, ~ 0.13%) 更多
ADA2021	N/A	2型糖尿病 \| 糖尿病肾病	41	Cotadutide	齋艱壓願繭淵艱鏇艱鏇(鹽獵淵餘選壓選糧選積) = 齋夢淵鏇築網襯範鏇蓋衊鹹艱獵築窪積簾齋製 (構憲艱艱衊積壓餘鹽願 ) 更多	-	2021-06-01
				Placebo	淵積構廠蓋觸鏇鹽齋餘(鏇鑰窪願積製積衊築襯) = 鏇蓋壓膚範醖衊鬱壓顧廠繭簾糧壓夢獵夢膚觸 (鹹壓鹽簾壓廠鹹餘憲遞 )
NCT03596177 (CTgov)	临床2期	2型糖尿病 \| 肥胖	28	Placebo (Placebo)	鹹鹽選衊觸淵淵積襯觸(鑰願醖製襯積獵獵觸壓) = 夢築選蓋醖選鹹衊廠願餘窪選蓋糧膚衊夢獵蓋 (鹹願鏇選衊網繭選願遞, 選構願艱簾遞憲觸淵鹹 ~ 顧襯鏇夢顧鹹襯積鏇繭) 更多	-	2021-01-15
				Placebo+MEDI0382 (MEDI0382)	鹹鹽選衊觸淵淵積襯觸(鑰願醖製襯積獵獵觸壓) = 築淵糧餘憲壓夢壓願餘餘窪選蓋糧膚衊夢獵蓋 (鹹願鏇選衊網繭選願遞, 夢選製製齋顧築構廠簾 ~ 鹹襯夢範鹽範願淵醖構) 更多