The two main aims of this clinical study is;
1. To investigate if the results from a series of physiological tests and questionnaires prior to treatment, can be used to predict the treatment response to obesity medication
2. To investigate the effect of combining semaglutide and pramlintide on various aspects of appetite, food preference and eating habits.
The study is planed as a 26 week, double blinded, randomized, placebo controlled trial. The goal is to include N=40. They will all receive weekly semaglutide injections. After 24 weeks they will be randomized to receive either an amylin analog (pramlintide) or placebo as a continuous infusion for two weeks, in addition to weekly semaglutide.
The results from this study will contribute to identifying possible predictors of treatment response, enabling optimal individualized medical weight loss treatment. As well as providing knowledge on the complex interplay between incretin hormones and their effects on appetite and eating habits.

开始日期2024-10-01

申办/合作机构-

NCT06186063

/ RecruitingN/AIIT

The Role of Amylin in Bone Metabolism

The clinical study aims to investigate the effect of the intravenously administrated amylin analogue (pramlintide) on the circulating levels of C-terminal telopeptide of type I collagen (CTX-1) (a marker of bone resorption) and N-terminal propeptide of type I procollagen (P1NP) (a marker of bone formation) in individuals with type 1 diabetes and matched healthy controls during fasting euglycemic conditions.

开始日期2024-02-12

申办/合作机构-

NCT06046417

/ Recruiting临床2/3期IIT

A Randomized, Controlled, Crossover Trial to Assess a Fully Automated, Dual-hormone (Insulin-and-pramlintide) Delivery System Without Carbohydrate Counting in Regulating Glucose Levels in Adults With Type 1 Diabetes.

The aim of this clinical trial is to investigate whether a fully automated Lyumjev-and-pramlintide delivery system improves glycemic outcomes in adults with type 1 diabetes. The main question we aim to answer is whether a Lyumjev-pramlintide fully closed loop system improves time in range compared to a hybrid closed loop system with carbohydrate counting. We also aim to find the optimal insulin to pramlintide ratio for glycemic control in the fully automated system.
In this cross-over study, patients will undergo the following three interventions in a random order:
(i) fully automated Lyumjev insulin-and-pramlintide (8 μg/u) (ii) fully automated Lyumjev insulin-and-pramlintide (10 μg/u) (iii) rapid automated Lyumjev insulin-and-placebo with carbohydrate-matched boluses
For all interventions, participants will be required to wear two Ypsomed pumps programmed by our developed EuGlide system.

开始日期2023-11-30

申办/合作机构

Mcgill University Health Centre

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100 项与醋酸普兰林肽相关的临床结果

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100 项与醋酸普兰林肽相关的转化医学

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100 项与醋酸普兰林肽相关的专利（医药）

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项与醋酸普兰林肽相关的文献（医药）

2024-12-01·Archives of Biochemistry and Biophysics

Development of the novel amylin and calcitonin receptor activators by peptide mutagenesis

Article

作者: Lee, Sangmin

The amylin peptide hormone receptor is the complex of the calcitonin peptide hormone receptor and an accessory protein. The calcitonin receptor activation controls calcium homeostasis, while it also functions as the main component of the amylin receptor. Amylin receptor activation in brains controls blood glucose and appetite. Currently, non-selective amylin and calcitonin receptor activators have been tested for body weight reduction to treat obesity. Here, multiple peptide activators for human amylin and calcitonin receptors were developed by introducing comprehensive mutagenesis to rat amylin peptide. The rat amylin peptide C-terminal fragment that interacts with amylin receptor extracellular domain was used to screen for affinity-enhancing mutations. Up to twelve mutational combinations were found to significantly increase peptide affinity both for amylin and calcitonin receptor extracellular domains by over 100-fold. Using these affinity-enhancing mutations, three representative rat amylin analogs with thirty-seven amino acids were made to test the potency increase for amylin and calcitonin receptor activation. All three mutated rat amylin analogs showed significant potency increases by 5- to 10-fold compared to endogenous rat amylin. These mutated peptide activators also showed higher potency for human amylin and calcitonin receptor activation than a clinically available amylin receptor activator pramlintide. These amylin and calcitonin receptor activators developed in this study may be useful as the valuable pharmacological tools that activate amylin receptors in cell-based systems.

2024-12-01·International Journal of Pharmaceutics

A microfluidic in vitro method predicting the fate of peptide drugs after subcutaneous administration

Article

作者: Hansson, Per ; Hanafy, Belal I. ; Abrahmsén-Alami, Susanna ; Mazza, Mariarosa ; Wanselius, Marcus ; Hanafy, Belal I

For many biopharmaceuticals, subcutaneous (sc) administration is the only viable route. However, there is no in vitro method available accurately predicting the absorption profiles of subcutaneously injected pharmaceuticals. In this work, we show that a recently developed microfluidics method for interaction studies (MIS) has the potential to be useful in this respect. The method utilises the responsiveness of polyelectrolyte microgel networks to oppositely charged molecules as a means to monitor the interaction between peptides and hyaluronic acid (HA), a major constituent of the subcutaneous extracellular matrix. We use the method to determine parameters describing the strength of interaction between peptide and HA as well as the peptide's aggregation tendency and transport properties in HA networks. The results from MIS studies of the peptide drugs exenatide, pramlintide, vancomycin, polymyxin B, lanreotide, MEDI7219 and AZD2820 are compared with results from measurements with the commercially available SCISSOR system and in vivo absorption and bioavailability data from the literature. We show that both MIS and SCISSOR reveal differences in the peptides' diffusivity and tendency to aggregate in the presence of HA. We show that MIS is particularly good at discriminating between peptides forming aggregates stabilised by non-electrostatic forces in the presence of HA, and peptides forming complexes stabilised by electrostatic interactions with HA. The method provides two parameters that can be used to quantify the peptides' aggregation tendency, the one describing the peptide packing density in complexes with HA and the other the apparent diffusivity upon release in a medium of physiological ionic strength and pH. The order of the peptides when ranked by increasing binding strength at pH 7.4 determined with MIS is shown to be in agreement with the order when ranked by the apparent 1st order absorption rate constant (k_a) after sc administration in humans: lanreotide (Autogel) < exenatide (IRF) < AZD2820 < pramlintide < lanreotide (IRF) (IRF: Immediate release formulation). A correlation is found between the 1st order release rate constant determined with SCISSOR and k_a for lanreotide (Autogel), exenatide and AZD2820. A mechanism relating the magnitude of k_a to the peptides' charge is proposed.

2024-11-01·International Journal of Biological Macromolecules

Intranasal administration of dextran-pramlintide polyelectrolyte complex-coated nanoemulsions improves cognitive impairments in a mouse model of Alzheimer's disease

Article

作者: França, Angela P ; de Souza, Bruna S. ; Agnes, Jonathan P. ; França, Angela P. ; Prediger, Rui D ; Agnes, Jonathan P ; Lemos-Senna, Elenara ; Zuglianello, Carine ; Prediger, Rui D. ; de Souza, Bruna S

Nasal delivery has emerged as a non-invasive route to administer drugs for brain delivery. In particular, polyelectrolyte complexes-based nanocarriers have been demonstrated to be advantageous for nasal delivery of peptide drugs and vaccines. Pramlintide (Pram) is a peptide that emerges as a novel neuroprotective strategy to modify the pathogenesis of Alzheimer's disease (AD). In this study, we examined the effects of the intranasal administration of dextran-pramlintide polyelectrolyte complex-coated nanoemulsions (PEC-NE_DexS/Pram) in an experimental model of AD induced by intracerebroventricular (i.c.v.) infusion of amyloid-beta (Aβ₁_-₄₂) peptide in mice. PEC-NE_DexS/Pram displayed droplet size lower than 200 nm and a negatively charged surface. The locomotor activity of the animals was not affected by the i.c.v. Aβ₁_-₄₂ injection or Pram treatment. On the other hand, the intranasal administration of PEC-NE_DexS/Pram at a dose of 100 μg/day for 14 consecutive days restored the impairment induced by Aβ₁_-₄₂ injection in the discriminative learning and the short-term spatial reference memory of mice. However, Pram treatment did not alter the Aβ₁_-₄₂-induced anhedonic behavior, oxidative stress parameters, or the pre-synaptic SNAP-25 and post-synaptic PSD-95 levels in the hippocampus and prefrontal cortex. These findings indicate cognitive-enhancing properties of intranasal Pram administration in an animal model of AD.

项与醋酸普兰林肽相关的新闻（医药）

2025-01-12

·药时代

全网寻找Amylin口服产品 | 药时代BD项目

正文共： 3000字 3图预计阅读时间： 8分钟 Amylin作为针对肥胖和超重的新药研发热门靶点之一，正吸引着全球制药行业的高度关注。MNC公司、欧美biotech公司、欧美基金公司委托药时代帮助寻找靶向Amylin受体的小分子新药产品或可口服的多肽产品等其他分子实体，目前所处阶段最好是PCC已经确定。我们诚挚邀请感兴趣的公司推荐更多靶向Amylin受体的小分子新药产品或可口服的多肽产品等其他分子实体。如果您有相关产品或信息，请速速联系药时代BD团队，邮箱：BD@drugtimes.cn 让我们共同推动Amylin靶点新药的研发，为肥胖和超重患者带来更多的治疗选择。以下内容仅供参考，欢迎批评指正！衷心感谢！~ Amylin作为肥胖新药研发的靶点的作用机理 Amylin（胰淀素）是一种由37个氨基酸组成的多肽激素，由胰岛β细胞分泌，与胰岛素一起在餐后被释放到血液中。它在代谢调节中发挥重要作用，特别是在控制食欲和能量平衡方面。以下是Amylin作为肥胖新药研发靶点的主要作用机理：抑制食欲： Amylin通过作用于大脑中的食欲调节中枢，减少食欲，增加饱腹感，从而减少食物摄入。这种作用机制有助于控制过度饮食，减少能量摄入。延缓胃排空： Amylin能够抑制肠胃蠕动，延缓胃排空速度。这不仅增加了饱腹感，还减少了食物在胃中的停留时间，从而进一步控制食物摄入。抑制胰高血糖素分泌： Amylin可以抑制胰高血糖素的分泌，从而减少肝脏中的葡萄糖生成，帮助调节血糖水平。这一机制对于控制餐后血糖升高尤为重要。增加能量代谢： Amylin通过多种机制增加机体的能量代谢，包括促进脂肪氧化和减少脂肪组织重量。这有助于减少体内脂肪积累，从而达到减重的效果。改善瘦素应答： Amylin可以改善瘦素的应答，增强瘦素在调节能量平衡和体重管理中的作用。瘦素是一种重要的食欲调节激素，通过改善瘦素应答，Amylin进一步增强了减重效果。抑制胃酸分泌： Amylin能够抑制胃酸分泌，减少胃部不适，从而间接影响食欲和食物摄入。这一机制有助于减少因胃部不适引起的过度进食。Amylin的代谢调节功能主要通过胰淀素受体（Amylin receptors, AMYRs）介导完成。胰淀素受体是一类特殊的蛋白异二聚体，由降钙素受体（Calcitonin receptor, CTR）和受体活性修饰蛋白（Receptor-Activity Modifying Protein, RAMPs）形成。RAMPs分为三种亚型：RAMP1、RAMP2和RAMP3，分别与CTR形成AMY1、AMY2和AMY3三种亚型的受体。临床应用主要包括以下方面。 Pramlintide： Pramlintide是首个获批用于糖尿病管理的合成胰淀素类似物，具有类似于GLP-1受体激动剂的减肥效果。它通过模拟天然胰淀素的作用机制，参与调控食欲、减缓胃排空速度以及改善血糖控制。然而，其疗效有限且与恶心和低血糖等副作用相关，妨碍其在临床上的广泛使用。 Cagrilintide： Cagrilintide是一种新型长效胰淀素类似物，在二期临床试验中，每周一次给药方案下的Cagrilintide呈现出剂量依赖性的体重减轻作用，其效果介于6%至10.8%之间。相比之下，同样为3毫克剂量的利拉鲁肽带来的体重减轻为9%，而安慰剂组则只有3%的减轻幅度。 Amycretin： Amycretin是一款GLP-1R和胰淀素受体的长效协同激动剂，正在开发皮下注射（每周一次）和口服（每天一次）两种剂型，目前拟开发适应症为肥胖。一项包含16位患者的口服Amycretin小型1期试验表明，患者在接受治疗12周后其体重下降幅度达13.1%，相较之下，安慰剂组患者的体重下降幅度仅为1.1%。此外，Amycretin展现良好的药代动力学特性，以及与其所开发的GLP-1类疗法类似的良好安全性、耐受性以及不良反应。Amylin通过多种机制调节食欲、延缓胃排空、抑制胰高血糖素分泌、增加能量代谢和改善瘦素应答，从而在肥胖和糖尿病治疗中发挥重要作用。随着对Amylin受体的深入研究，靶向Amylin的新药研发正在快速推进，未来有望为肥胖和糖尿病患者提供更有效的治疗选择。 Amylin新药相关交易简介 1. 百时美施贵宝收购Amylin Pharmaceuticals 2012年，百时美施贵宝以50亿美元的价格收购了Amylin Pharmaceuticals。Amylin Pharmaceuticals是一家专注于糖尿病诊断和治疗产品的生物制药公司，其新药Bydureon（每周注射一次的糖尿病治疗用药）具有年销售额15亿美元的潜力。2. 诺和诺德的Amycretin 2024年3月7日，诺和诺德在投资者日活动上汇报了其减重管线的布局和进展，特别引人注目的是口服Amycretin。这是一种GLP-1R和Amylin受体激动剂，一期临床中治疗12周减重13.1%，远优于司美格鲁肽治疗12周减重6%的效果。这一数据推动了诺和诺德股价盘前涨近6%，市值逼近6000亿美元。3. Zealand Pharma的Petrelintide 2024年6月21日，丹麦制药公司Zealand Pharma公布了其减肥注射剂Petrelintide的积极试验结果，引发市场热烈反响，股价飙升20%。Petrelintide属于长效Amylin类药物，在减重和稳定血糖方面显示出良好前景。1B期MAD试验结果显示，接受高剂量Petrelintide治疗的参与者平均体重下降了8.6%，而安慰剂组体重仅下降了1.7%。4. 礼来与KeyBioscience的合作 2024年10月10日，瑞士KeyBioscience和礼来公司宣布扩大在开发双胰淀素（Amylin）和降钙素（Calcitonin）受体激动剂（DACRA）方面的合作。DACRA是一种新型的双受体激动剂，旨在通过双重机制增强食欲抑制，实现更好的减重效果。5. 先为达生物与Verdiva Bio的合作 2025年1月10日，先为达生物宣布与Verdiva Bio达成了一项全球开发和商业化许可与合作协议，涉及每周一次口服GLP-1受体激动剂伊诺格鲁肽等3款产品组合，总金额高达24.7亿美元。Verdiva Bio是一家专注于开发针对肥胖和其他心血管代谢紊乱的创新疗法的公司，刚刚完成4.11亿美元A轮融资。此次合作的产品组合包括：口服伊诺格鲁肽（Ecnoglutide Oral, XW004）：处于II期临床试验准备阶段的潜在同类首创的每周一次口服GLP-1受体激动剂。口服胰淀素受体激动剂（Amylin RA）：处于临床前阶段的潜在同类首创的每周一次口服胰淀素受体激动剂，可用作单药治疗或与GLP-1受体激动剂联合使用。皮下注射胰淀素受体激动剂（Amylin RA）：处于临床前阶段的潜在同类最佳的长效皮下注射胰淀素受体激动剂，可用作单药治疗或与GLP-1受体激动剂联合使用。这些交易和合作表明，Amylin作为肥胖和糖尿病治疗的新靶点，正在吸引越来越多的制药公司的关注和投资。通过这些合作和收购，制药公司希望利用Amylin的多重机制，开发出更有效的减重和降糖药物，满足市场对创新疗法的迫切需求。如果您有相关产品或信息，请速速联系药时代BD团队，邮箱：BD@drugtimes.cn 让我们共同推动Amylin靶点新药的研发，为肥胖和超重患者带来更多的治疗选择。参考资料：各家公司官网药时代数据库其它公开信息推荐阅读美国上市公司寻找创新性ADC、双抗，您感兴趣吗？| 药时代BD项目 2024-07-25 诺和、礼来看好的ADC payload，您感兴趣吗？| 药时代BD项目 2024-07-22 药时代BD-030项目 | IND ready阶段月制剂减重药物GDF15融合蛋白寻求合作 2024-06-25 药时代BD需求 | 顶级MNC寻找优质项目：炎症性肠病、哮喘、慢阻肺、特发性肺间质纤维化 2024-05-03 版权声明/免责声明本文为汇编文章。本文仅作信息交流之目的，不提供任何商用、医用、投资用建议。文中图片、视频、字体、音乐等素材或为药时代购买的授权正版作品，或来自微信公共图片库，或取自公司官网/网络，部分素材根据CC0协议使用，版权归拥有者，药时代尽力注明来源。如有任何问题，请与我们联系。衷心感谢! 药时代官方网站:www.drugtimes.cn 联系方式: 电话:13651980212 微信:27674131 邮箱:contact@drugtimes.cn 点击这里，查看更多精彩内容！

2025-01-10

·PRNewswire

Iktos and Cube Biotech Announce Launch of Small Molecule AI Drug Discovery Collaboration

Partnership will leverage Iktos's AI-enabled drug discovery platform and Cube Biotech's advanced protein technologies to develop novel agonists of the Amylin Receptor PARIS and MONHEIM, Germany, Jan. 10, 2025 /PRNewswire/ -- Iktos, a leader in Artificial Intelligence (AI) and Robotics for drug design, and Cube Biotech, a pioneer in membrane protein production and purification technologies, today announced a strategic collaboration to discover novel small molecule agonists of the Amylin Receptor. The partnership combines Iktos' generative AI-driven drug discovery and robotic synthesis platform with Cube Biotech's advanced native membrane protein technology NativeMPTM, as well as their purification and biophysical assay expertise, to accelerate the development of breakthrough therapies. This paves the way for a joint collaborative offering directed towards pharmaceutical companies, combining the strengths of both platforms to undertake their most challenging drug discovery programs. Amylin receptor agonists hold significant promise for addressing unmet medical needs in cardiometabolic disorders, including obesity, diabetes, and metabolic dysfunction-associated steatotic hepatitis (MASH). The Amylin Receptor regulates appetite and satiety, making it a compelling target for obesity, which affects over one-third of the global population. Existing GLP-1 receptor agonist therapies like semaglutide or the peptide Amylin analogue Pramlintide have limited impact due to high costs, accessibility, and undesirable side effects. Orally administered novel small molecule agonists of the Amylin receptor could overcome these barriers, offering scalable and effective treatments and providing better management for the growing obesity epidemic and its comorbidities. However, the receptor's structural and biological complexity has long posed challenges for discovering viable low-molecular-weight modulators. "By tackling one of the most pressing unmet needs in cardiometabolic disorders, our partnership with Cube Biotech aims to discover improved treatments for patients affected by obesity, diabetes, and related conditions," said Yann Gaston-Mathé, Co-founder and CEO of Iktos. "We are excited to add the Amylin Receptor to our pipeline as this complex, yet promising target demands innovation at every stage. We see this collaboration as a foundation for future initiatives, extending the reach of our combined platform to address the most challenging membrane targets for the benefit of our pharma partners." Iktos has developed a cutting-edge 3D generative chemistry technology for structure-guided de novo design that natively accounts for protein flexibility during molecule optimization—a key advantage over models like AlphaFold, which can only be applied post-molecule generation. Cube Biotech has developed a world-leading protein production platform, based on NativeMP™ technology, which preserves the natural configuration of membrane proteins - a key advantage in accessing biologically active drug targets for testing. The company's native protein stabilization technology enhances the reliability and precision of functional assays, structural insights, and downstream applications. "Amylin Receptor is a challenging but highly promising target for metabolic disorders", said Dr. Barbara Maertens, Co-founder and COO of Cube Biotech. "Through our collaboration with Iktos, we aim to leverage our advanced protein stabilization and structural analysis technologies to validate and accelerate the discovery of novel small molecule agonists. Together, we are setting a new standard for efficiency and innovation in drug discovery." These integrated technologies endeavor to overcome longstanding inefficiencies in drug discovery, shortening timelines, improving success rates, and unlocking new possibilities for targeting complex and historically elusive membrane proteins, such as G-protein coupled receptors (GPCRs), membrane transporters, ion channels, and others. About Iktos Iktos is a leader in artificial intelligence and robotic solutions applied to research in medicinal chemistry and new drug design. Iktos' proprietary and innovative generative AI solution enables the design of molecules that are optimized in silico to meet all the success criteria of a small molecule discovery project. The use of Iktos technology enables major productivity gains in upstream pharmaceutical R&D. Iktos offers its technology through the SaaS software platforms Makya™ for generative drug design and Spaya™ for retrosynthesis, and through strategic collaborations with pharma companies where Iktos mobilizes its unique platform and leading-edge capabilities to expedite small molecule drug discovery for the benefit of its partners. Iktos has also developed Iktos Robotics, a unique AI-driven synthesis automation platform that dramatically accelerates the Design-Make-Test-Analyze cycle in drug discovery and is developing its own pipeline of drug candidates targeting oncology and auto-immune and inflammatory diseases. In March 2023, Iktos completed a 15.5M€ Series A financing round co-led by M Ventures and Debiopharm Innovation with contribution by Omnes Capital. In July 2024, Iktos announced the acquisition of Synsight, thereby complementing its Chemistry AI platform with a groundbreaking biology platform for the discovery of new drugs targeting Protein-Protein Interactions (PPI) and RNA-Protein Interactions (RPI). About Cube Biotech Cube Biotech is a leader in membrane protein production, purification, and characterization technologies. With proprietary copolymer-based solutions that maintain biological integrity in native-like protein states, Cube Biotech enables groundbreaking research in challenging drug targets, including membrane receptors, protein co-expressions, and even larger complexes. The company's expertise in assay development, biophysical characterization, and structural resolution supports efficient drug discovery workflows across the pharmaceutical and biotechnical industries. Additionally, an extensive purification resin and magnetic bead portfolio for affinity chromatography and efficient protein purification is manufactured in-house at high quality. For more information, visit . Media Contact: Eleonora Echegaray P: 35 823189279 E: [email protected] SOURCE Iktos WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

并购

2024-12-25

·CPHI制药在线

平行世界中，诺和诺德新一代减肥药CagriSema命运启示录

关注并星标CPHI制药在线云移稚尾开宫扇，日绕龙鳞识圣颜。一卧沧江惊岁晚，几回青锁点朝班。杜甫的这首《秋兴其五》追忆的是长安宫殿巍峨庄严，早朝场面庄严肃穆，反衬如今的萧索落魄盛况不在。这样的描述竟然也有些契合诺和诺德的III期管线减肥候选药CagriSema。 01 CagriSema，天将降大任于斯药？ CagriSema是诺和诺德的第三代减肥药管线资产，上承Saxenda（liraglutide）与Wegovy（semaglutide），寄托着诺和诺德对巩固和扩大减肥药市场统治地位的未来希望。CagriSema是一款联合疗法，其有效成分包括cagrilintide和semaglutide。Cagrilintide是一种胰淀素（Amylin）类似物，而semaglutide是Wegovy和Ozempic的有效成分。CagriSema设计用于每周一次的皮下注射，主要用于治疗肥胖、2型糖尿病和MASH（代谢功能障碍相关脂肪性肝炎）。 CagriSema的治疗策略建立在两种成分强效互补的机制之上。Cagrilintide作为胰淀素受体激动剂，显著抑制食欲并有效延缓胃排空。胰淀素是一种与胰腺β细胞共同分泌的肽，功能与GLP-1相似，既能够强力减缓胃排空，又能显著提升饱腹感，尽管它不会直接刺激胰岛素的分泌。而Semaglutide作为GLP-1受体激动剂，不仅大幅增强胰岛素分泌，还强力抑制胰高血糖素的释放，同时进一步减缓胃排空。这两者的联合作用，使CagriSema在血糖控制和体重管理方面具备卓越的效果，并可能为治疗MASH提供重要的突破。 CagriSema直接跳过了肥胖症的II期试验，得益于其核心成分cagrilintide和semaglutide此前已分别在肥胖症领域进行了临床研究。2022年，诺和诺德启动了CagriSema用于肥胖症的III期临床研究REDEFINE 1。Semaglutide的巨大成功早已让投资者期望值居高不下，这使得CagriSema处于一种"成败皆系一线"的局面：临床结果稍有不佳，其负面冲击将远远超过理想结果对股价的正向提振。所谓的"积极数据"标准，对于CagriSema而言，已经意味着25%的减重率--这一数字几乎与减肥手术效果相媲美。而作为对比，Wegovy在其关键肥胖症试验中的减重率为15%，而礼来的Zepbound在72周后的减重率则达到23%左右。如此高的期望不仅源于减肥药市场竞争的激烈，更反映了投资者"望山跑死马"的心态，期望下一款药物能超越前者，带来更大的回报。分析师们已对此做出预测：如果CagriSema成功达到25%的减重目标，诺和诺德的股价预计将上涨10%，而礼来的股价可能受蝴蝶效应影响而下跌5%。然而，若CagriSema的减重效果没有达到这个预期，诺和的股价可能暴跌10%-20%；而如果表现更差，诺和的市值恐将瞬间蒸发20%-30%。 02 CagriSema困局：III期数据究竟成功还是不成功？事实正如投资者担心的那样，诺和诺德12月20日公布了人们翘首企盼的CagriSema的III期数据：减重率23%。虽然这个数据如果放在时间线的上游将是一个激动人心的数据，但对于胃口已经被Wegovy和Zepbound高高吊起的投资者们来说，这个数据几乎与失败等同。于是诺和的股价在12月20日一开盘便决绝地如同分析师们当初的预测那样暴跌20% (图1)。图1. 诺和诺德股价在CagriSema III期数据公布前后走势图。（图片来源：Nordnet）诺和诺德上周五公布的数据显示，在III期研究中，CagriSema治疗组的患者在68周时平均减重20%（包括退出的患者）。如果只考虑坚持治疗的患者，减重比例达到23%。包括退出的患者在内，单独使用semaglutide的患者减重15%，使用cagrilintide的患者减重12%，而安慰剂组患者仅减重3%。在试验中，患者被允许调整剂量。68周时，CagriSema组有57%的患者使用最高剂量，而semaglutide组和cagrilintide组的这一比例分别为70%和83%。尽管联合疗法23%的结果已经相当不错，但却没有达到诺和诺德此前预计的25%的减重率。诺和诺德高层对于CagriSema的减重效果感到鼓舞，尤其是考虑到只有57%的受试者接受了最高剂量的事实。诺和诺德表示，CagriSema最常见的不良反应是胃肠道反应，且大多数为轻度至中度，并随着时间的推移有所减轻，这与GLP-1药物类别中的其他治疗反应相似。他们计划进一步探索CagriSema的额外减重潜力。CagriSema未来的试验设计包括一个为期两年的延长期，在此阶段，参与者将不接受任何治疗，诺和诺德计划研究CagriSema的效果能持续多久。 03 CagriSema遭受质疑，诺和何去何从？随着竞争对手，尤其是礼来等公司快速开发出具有良好减重效果的新药物，诺和诺德正面临日益加剧的压力，因此CagriSema肩负了他们最大的期望。诺和诺德正在进行一项与Zepbound的头对头试验。分析师指出，这表明诺和诺德可能认为CagriSema有望成为比Zepbound更有效的产品。 CagriSema在公布III期结果之前，诺和诺德就已经处在了极大的压力之下，这一点从他们低迷的股价走势就可窥见一斑。面临极大压力的诺和诺德需要证明 CagriSema将成为下一款令人高山仰止的重磅炸弹减肥药。考虑到礼来在诺和公布CagriSema III期数据之前就已经向公众展示了他们的Zepbound在一项头对头试验中优于Wegovy的最新结果，诺和对CagriSema扳回一城的期待就已经拉满。投资者希望CagriSema能展现出显著优于Zepbound的减重成绩，但20-23%的结果相对于Zepbound来说几乎没有优势，况且礼来管线中号称3G减肥药的retatrutide已经在其II期研究中取得了24%的减重效果，他们的管线中还有一款小分子GLP-1减肥药orforglipron。诺和诺德这边，CB1受体抑制剂减肥候选药monlunabant在IIa期试验中的表现不愠不火，10 mg最低剂量16周的平均减重率为6.4%（安慰剂组0.6%），20和50 mg的试验也在进行之中，诺和这项去年以11亿美元从Inversago Pharmaceuticals收购的项目的期待是"恰当时间"的15%减重率。 04 CagriSema对于胰淀素类似物集团影响几何？ CagriSema的"偶失龙头望"，对于其有效组分之一的cagrilintide背后的胰淀素类似物的减肥药候选物集团将产生怎样的影响？在减肥药物开发的征途上，很多制药公司选择了胰淀素受体作为开发靶点。一些开发商表示，胰淀素类似物药物不仅可以显著减轻体重，而且与 GLP-1 类药物相比，恶心和呕吐的发生率也更低。胰淀素类似物的药物非专有名大多数是以lintide作为结尾的，例如阿斯利康已经上市的2型糖尿病多肽药物pramlintide，诺和诺德的cagrilintide，以及Zealand Pharma的petrelintide。礼来也在针对胰淀素类似物进行开发。目前胰淀素类似物减肥后选药中最令人关注的是Zealand Pharma的petrelintide。今年6 月，Zealand Pharma公布了 petrelintide的 Ib 期顶线结果，在 16 周剂量后，平均体重减轻高达 8.6%（经安慰剂调整后为 6.9%）。这个结果优于诺和诺德的胰淀素类似物候选药物 cagrilintide ，后者在其 II 期研究中实现了 5.0% 的体重减轻。Petrelintide的额外优势在于其在最高测试剂量下仍可耐受，在安全性表现方面远高于 cagrilintide 的研究结果。美国银行分析师在Zealand Pharma公布三季度财报的同一天表示，他们预计petrelintide将主要用于 GLP-1 不耐受或失败市场（约占 20% 的患者），并预计其年销售额将达到 80 亿美元的峰值。 CagriSema的III期临床读数令petrelintide殃及池鱼，使一部分人怀疑其作为胰淀素类似物的减重潜力，这一点从Zealand Pharma的股价同样在12月20日这一天暴跌（后又发生了回弹，Zealand股价暴跌背后的主要原因应该是他们的针对短肠综合症的GLP-2药物glepaglutide的NDA申请被FDA拒绝）可见一斑（图2）。然而Zealand Pharma的首席执行官Adam Steensberg 在接受采访时表示，他仍然相信胰淀素类似物的策略，并对 CagriSema 数据感到鼓舞。图2. Zealand Pharma股价最近走势图。（图片来源：Nordnet）在CagriSema的试验中，仅服用cagrilintide的患者体重减轻了 12%。Steensberg 估计，petrelintide 对胰淀素受体的活性比cagrilintide高 9 倍，因此可以减轻更多体重。他表示，CagriSema 的结果证实了 Zealand 针对petrelintide 设定15% 至 20% 的长期减重率目标的合理性。此外，在cagrilintide组中，83% 的患者服用最高剂量，而semaglutide组为 70%，CagriSema 组为 57%。Steensberg 说，这表明患者最能耐受cagrilintide，这同样支持了Zealand 的观点，即针对胰淀素受体开发的减肥药可以减少胃肠道副作用。 05 药物开发与华尔街，哪个才是修罗场？ CagriSema试验"叫好不叫座"的现象同时表明了投资者在针对减肥药投资过程中的浮躁心态，23%的减重率在世亦时移的情况下竟然成为了诺和诺德股价暴跌的因素，这在几年前是不可想象的情况。股票的大幅波动表明投资者是多么关心 CagriSema 能否实现至少 25% 的减肥目标。但一些分析师质疑这些预期是否符合患者的实际需要，在现有减重率已经逼近手术减肥效果的情况下，单纯地追求个位数的增长效果是否合理。瑞穗分析师Holz表示，已上市的减肥药对于绝大多数的患者来说已经足够好了，并且怀疑正在开发的下一代减肥药是否真的有更大的用途。Holz认为，CagriSema的结果警示人们，必须降低对新肥胖候选药物减肥水平的预期。下一个竞争领域应该是围绕开发更耐受、副作用更小的减肥药物，以及可以轻松大规模生产的口服治疗药物展开。多伦多大学教授Dan Drucker也认为，CagriSema 等新疗法在现实世界中帮助患者的潜力与投资者对它们的看法之间存在脱节。Drucker明心见性地表示，"这些药物仍然非常好，只是我们生活的世界被华尔街最大化追求减重率而驱动。" Drucker还指出，减肥药的实际贡献不应该狭隘地仅仅通过减重率来衡量，例如semaglutide对于预防心血管问题的功效可能部分来自于与减重无关的机制。Druck教授称，"我们的目标是改善健康。有大量新证据表明，GLP-1 药物改善健康的益处，包括减少心脏病发作、中风、心血管死亡和肾脏疾病，这些与减肥基本无关。因此，我们对 25%、23% 和 22% 减重率的另眼相看可能在改善健康的背景下没有意义。" CagriSema"功成而弗居"的现象意味着，人们可能生活在两个并行的世界之中，一个由科学引领，而另一个则由资本驱动。 Ref. Chen, E. Next-gen obesity treatment from Novo Nordisk misses mark in pivotal trial. STAT. 20. 12. 2024. Armstrong, A. Novo's Next-Gen CB1 Drug Leads to Weight Loss in Phase II, but Neuropsychiatric Events Reported. Biospace. 20. 09. 2024. Chen, E. Novo's new obesity drug shows modest results, raises concerns of psychiatric side effects. STAT. 20. 09. 2024. Chen, E. What Novo Nordisk's disappointing trial results mean for the obesity drug market. STAT. 20. 12. 2024. END 【智药研习社近期直播】来源：CPHI制药在线声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。投稿邮箱：Kelly.Xiao@imsinoexpo.com ▼更多制药资讯，请关注CPHI制药在线▼ 点击阅读原文，进入智药研习社~

临床3期临床结果放射疗法

100 项与醋酸普兰林肽相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D05595	醋酸普兰林肽	A10BX05	DB01278

研发状态

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适应症	国家/地区	公司	日期
1型糖尿病	美国	AstraZeneca AB	2005-03-16
2型糖尿病	美国	AstraZeneca AB	2005-03-16

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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1期	美国	AstraZeneca PLC	2004-08-01
2型糖尿病	临床前	美国	Amylin Pharmaceuticals, Inc.	2010-05-01
胰岛素依赖型糖尿病2	临床前	美国	AstraZeneca PLC	2003-04-01

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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


ADA2023	N/A	-	11	Faster aspart with CC	壓遞蓋膚醖餘範淵築鏇(簾構選觸鏇淵廠壓襯構) = 窪襯鬱觸繭醖鏇遞淵襯築蓋膚遞範築壓衊齋淵 (齋積鏇選積壓襯觸壓艱 )	-	2023-06-20
				Faster aspart and pramlintide at a 1u:8µg ratio without CC	壓遞蓋膚醖餘範淵築鏇(簾構選觸鏇淵廠壓襯構) = 醖顧廠蓋網鹹淵蓋願艱築蓋膚遞範築壓衊齋淵 (齋積鏇選積壓襯觸壓艱 )
ADA2022	N/A	1型糖尿病	-	Fiasp and placebo with CC	顧鹽齋膚製齋壓糧製簾(鑰網獵壓獵襯遞衊襯鬱) = 壓糧壓淵獵淵鏇鏇顧範遞醖鹹廠襯鏇築衊夢觸 (選鹹糧衊壓夢齋艱蓋構 )	-	2022-06-01
				Fiasp and pramlintide with MA	顧鹽齋膚製齋壓糧製簾(鑰網獵壓獵襯遞衊襯鬱) = 範鹽積壓積選蓋醖壓廠遞醖鹹廠襯鏇築衊夢觸 (選鹹糧衊壓夢齋艱蓋構 )
NCT01841359 (CTgov)	临床4期	低血糖 \| 胃病	22	Pramlintide (Baseline (Prior to Pramlintide Treatment) Mixed Meal #1)	艱願積範餘遞網選蓋醖(鬱構鹽鬱顧顧淵鹽繭鏇) = 選積廠鹽壓獵鹽願壓醖獵選遞齋構蓋鏇衊窪齋 (範餘壓選襯網繭蓋鬱壓, 淵淵襯淵遞衊鹹積鑰廠 ~ 餘簾鹽範獵鏇餘鹽積遞) 更多	-	2022-05-26
				Pramlintide (Pramlintide - Mixed Meal #2)	艱願積範餘遞網選蓋醖(鬱構鹽鬱顧顧淵鹽繭鏇) = 鏇醖膚憲願膚顧夢鑰艱獵選遞齋構蓋鏇衊窪齋 (範餘壓選襯網繭蓋鬱壓, 鹹衊願壓廠膚衊蓋觸製 ~ 廠夢顧願遞糧窪廠膚構) 更多
ADO09 (EASD2019)	N/A	1型糖尿病	24	ADO09	(遞襯鹽襯獵繭選繭鏇獵) = 3 with ADO09, 2 with Ins&Pram 繭築膚窪艱構願鑰選築 (襯鬱選簾願願願遞艱鏇 ) 更多	积极	2019-09-18
				Insulin lispro
NCT02500979 (CTgov)	临床1期	1型糖尿病	34	Insulin (Placebo & Regular Insulin)	壓窪膚憲壓鏇鏇顧壓襯(獵願積鹹艱願憲艱簾齋) = 蓋鬱齋憲範選獵襯鬱鬱蓋醖餘壓鬱願鏇鑰鬱繭 (鹽糧餘糧淵顧網製網衊, 憲鹽餘構範廠鹽淵積鑰 ~ 鏇遞選蓋衊窪鬱膚窪遞) 更多	-	2018-11-02
				Insulin+Pramlintide (Pramlintide & Regular Insulin)	壓窪膚憲壓鏇鏇顧壓襯(獵願積鹹艱願憲艱簾齋) = 廠觸鏇觸獵襯鹹願膚糧蓋醖餘壓鬱願鏇鑰鬱繭 (鹽糧餘糧淵顧網製網衊, 範構窪繭築壓艱蓋齋範 ~ 繭製糧鑰範齋鹹憲遞顧) 更多
NCT02500979 (Pubmed \| Diabetes Care)	临床1期	1型糖尿病	34	Pramlintide	鏇艱鹹繭淵遞繭鏇壓鏇(醖鏇網餘窪範鹽夢衊膚) = 製夢選淵膚憲蓋餘襯鹽鬱築獵膚繭鹽築選築顧 (鏇選蓋鹹顧獵獵製壓願 )	-	2018-11-01
				Placebo	鏇艱鹹繭淵遞繭鏇壓鏇(醖鏇網餘窪範鹽夢衊膚) = 憲壓願鹹壓鹽齋網鏇淵鬱築獵膚繭鹽築選築顧 (鏇選蓋鹹顧獵獵製壓願 )
NCT00442767 (CTgov)	临床4期	1型糖尿病 \| 高血糖	8	Insulin (Rapid Acting Insulin Therapy - Before Meal)	(觸積憲願築夢壓獵餘鏇) = 鬱窪蓋鏇艱獵壓襯遞膚製膚顧網夢夢網窪網鑰 (醖築糧壓網餘襯糧醖鏇, 構糧繭壓醖齋簾膚糧壓 ~ 淵觸選簾襯糧醖鏇鬱製) 更多	-	2018-07-10
				Insulin+Pramlintide (Pre-meal Pramlintide and Post-meal Insulin Therapy)	(觸積憲願築夢壓獵餘鏇) = 繭範選築廠襯壓積餘壓製膚顧網夢夢網窪網鑰 (醖築糧壓網餘襯糧醖鏇, 艱願憲獵網鹹壓鹽窪網 ~ 鏇願鹹膚選廠糧衊鹹繭) 更多
NCT01269047 (CTgov)	临床4期	1型糖尿病 \| 高血糖	37	Insulin (Insulin Monotherapy)	顧構網獵蓋獵衊遞鑰鑰(齋膚夢襯夢衊餘獵鑰廠) = 鬱願鬱遞壓範襯憲鬱憲鹹襯廠選遞膚窪鏇廠鏇 (餘鑰鹹襯積鹽顧餘構鑰, 網壓構繭網窪獵窪夢糧 ~ 網網顧獵齋衊獵糧襯築) 更多	-	2018-02-08
				Pramlintide (Pramlintide + Insulin Group)	構獵遞鹽夢積襯糧蓋憲(壓顧艱網網齋構製顧築) = 顧鬱遞製繭膚觸顧築築鹽構鬱糧醖選壓願製淵 (艱艱壓夢鹽餘顧膚廠憲, 網願鹽齋膚窪醖鹹顧夢 ~ 鹽齋窪觸網積範壓鬱窪) 更多
NCT00392925 (CTgov)	临床2期	肥胖	177	Metreleptin (Metreleptin)	鹹製構鹽艱遞積蓋構積(鑰繭顧廠醖網餘齋獵鏇) = 鬱鬱繭憲鬱積願衊鬱範獵製鏇顧齋網築鏇獵鏇 (醖鏇構齋構鑰鑰觸獵製, 鏇簾繭繭襯積鏇餘鏇醖 ~ 觸餘鬱觸膚獵範構糧積) 更多	-	2014-02-28
				Pramlintide Acetate (Pramlintide Acetate)	鹹製構鹽艱遞積蓋構積(鑰繭顧廠醖網餘齋獵鏇) = 廠蓋醖艱艱衊醖鏇淵範獵製鏇顧齋網築鏇獵鏇 (醖鏇構齋構鑰鑰觸獵製, 鹹顧淵遞廠窪鹹淵齋鹹 ~ 窪鏇鏇憲鑰鹽餘積壓積) 更多