The purpose of this study is to determine if there is any difference in the way the body handles 3 types of evacetrapib tablets with different particle sizes. Information about any side effects will also be collected. This study will consist of 3 study periods. Participants will be dosed 3 times during the entire study. Each study period will consist of an inpatient stay for 3 days - the day before dosing (Day -1), dosing day (Day 1) and the day after dosing (Day 2). Then participants will be asked to return to the clinical research unit (CRU) daily for outpatient appointments up to Day 8. The overall length of this study is about 7 weeks from first dose to end of study. Screening will take place within 28 days prior to the first dose of evacetrapib and follow-up will take place 21 days after the last dose of evacetrapib.

开始日期2015-07-01

申办/合作机构

Eli Lilly & Co.

NCT02260648

/ Terminated临床3期

A Double-Blind Efficacy and Safety Study of Evacetrapib in Combination With Atorvastatin in Japanese Patients With Primary Hypercholesterolemia

The main purpose of this study is to evaluate the efficacy and safety of the study drug known as evacetrapib when administered in combination with atorvastatin for 12 weeks in Japanese participants with primary hypercholesterolemia.

开始日期2015-01-01

申办/合作机构

Eli Lilly & Co.

NCT02365558

/ Completed临床1期

Evaluation of the Impact of Increased Gastric pH Following Omeprazole Administration on the Pharmacokinetics of Evacetrapib in Healthy Subjects

The purpose of this study is to evaluate the effect of increased stomach pH on how much evacetrapib is found in the blood stream and how long the body takes to get rid of it when given to healthy participants. Information about any side effects that may occur will also be collected.
There are two parts to the study. Participation in both parts will be required.
The study will last approximately 30 days, not including screening.

开始日期2015-01-01

申办/合作机构

Eli Lilly & Co.

100 项与依塞曲匹相关的临床结果

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100 项与依塞曲匹相关的转化医学

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100 项与依塞曲匹相关的专利（医药）

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140

项与依塞曲匹相关的文献（医药）

2025-01-01·DRUG RESISTANCE UPDATES

CEA-induced PI3K/AKT pathway activation through the binding of CEA to KRT1 contributes to oxaliplatin resistance in gastric cancer

Article

作者: Tan, Song ; Li, Weihua ; Mi, Yulong ; Yang, Changshun ; Hong, Weifeng ; Lin, Shengtao ; Liu, Shaolin ; Chen, Yifan ; Chen, Yizhen

BACKGROUND:

The serum level of carcinoembryonic antigen (CEA) has prognostic value in patients with gastric cancer (GC) receiving oxaliplatin-based chemotherapy. As the molecular functions of CEA are increasingly uncovered, its role in regulating oxaliplatin resistance in GC attracts attention.

METHODS:

The survival analysis adopted the KaplanMeier method. Effects of CEA on proliferative capacity were investigated using CCK8, colony formation, and xenograft assays. Oxaliplatin sensitivity was identified through IC₅₀ detection, apoptosis analysis, comet assay, organoid culture model, and xenograft assay. Multi-omics approaches were utilized to explore CEA's downstream effects. The binding of CEA to KRT1 was confirmed through proteomic analysis and Co-IP, GST pull-down, and immunofluorescence colocalization assays. Furthermore, small molecule inhibitors were identified using virtual screening and surface plasmon resonance.

RESULTS:

Starting from clinical data, we confirmed that CEA demonstrated superior ability to predict the prognosis of patients with GC who received oxaliplatin-based chemotherapy, particularly in predicting recurrence-free survival based on serum CEA level. In vitro and in vivo experiments revealed CEA^high GC cells presented increased proliferative capacity and decreased oxaliplatin sensitivity. The resistance phenotype was transmitted through secreted CEA. Multi-omics analysis revealed that CEA activated the PI3K/AKT pathway by binding to KRT1, leading to oxaliplatin resistance. Finally, the small molecule inhibitor evacetrapib, which competitively inhibits the CEA-KRT1 interaction, was identified and validated in vitro.

CONCLUSIONS:

In summary, the CEA-KRT1-PI3K/AKT axis regulates oxaliplatin sensitivity in GC cells. Treatment with small molecule inhibitors such as evacetrapib to inhibit this interaction constitutes a novel therapeutic strategy.

2024-09-01·Cell Reports Medicine

Uncovering therapeutic targets for macrophage-mediated T cell suppression and PD-L1 therapy sensitization

Article

作者: Coussens, Lisa M ; Malhotra, Sanjay V ; Schedin, Pepper ; Lee, Jee Min ; Coussens, Lisa M. ; Malhotra, Sanjay V. ; Keefe, Bailey F ; Nelson, Dylan ; Dheeraj, Arpit ; Tailor, Dhanir ; Kumar, Sushil ; Kummar, Shivaani ; Stefan, Kirsten ; Li, Wenqi ; Keefe, Bailey F.

Tumor-associated macrophages (TAMs) and other myelomonocytic cells are implicated in regulating responsiveness to immunotherapies, including immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 axis. We have developed an ex vivo high-throughput approach to discover modulators of macrophage-mediated T cell suppression, which can improve clinical outcomes of ICIs. We screened 1,430 Food and Drug Administration (FDA)-approved small-molecule drugs using a co-culture assay employing bone-marrow-derived macrophages (BMDMs) and splenic-derived T cells. This identified 57 compounds that disrupted macrophage-mediated T cell suppression. Seven compounds exerted prominent synergistic T cell expansion activity when combined with αPD-L1. These include four COX1/2 inhibitors and two myeloid cell signaling inhibitors. We demonstrate that the use of cyclooxygenase (COX)1/2 inhibitors in combination with αPD-L1 decreases tumor growth kinetics and enhances overall survival in triple-negative breast cancer (TNBC) tumor models in a CD8⁺ T cell-dependent manner. Altogether, we present a rationalized approach for identifying compounds that synergize with ICI to potentially enhance therapeutic outcomes for patients with solid tumors.

2024-08-01·REGULATORY TOXICOLOGY AND PHARMACOLOGY

Evaluation of the EMA log kow trigger for fish BCF testing based on data for several human pharmaceuticals

Article

作者: Nfon, Erick ; Tell, Joan ; Nimrod Perkins, Alison ; Dolan, David G ; Davidson, Todd ; Häner, Andreas ; Ryan, James J ; Janer, Gemma ; Constantine, Lisa A ; Burden, Natalie ; Maynard, Samuel K ; Lee, Michael R

In the European Medicines Agency (EMA) "Guideline for Environmental Risk Assessment of Medicinal Products for Human Use," a fish bioconcentration factor (BCF) study is triggered in Phase I for pharmaceuticals having log Kow >4.5, to support Persistence, Bioaccumulation and Toxicity (PBT) screening, and in Phase II to assess secondary poisoning and bioaccumulation ('B') potential when log Kow ≥3. The standard sampling schedule outlined in OECD Test Guideline 305 (TG305) may require assessment of approximately 200 fish following exposure to low- and high-test concentrations and a negative control. We report experimental log Kow and BCF values for 64 human pharmaceuticals that were used to evaluate the current BCF testing trigger of log Kow ≥3, and whether a single BCF exposure concentration allows accurate classification of bioaccumulation potential. Our data support raising the BCF testing trigger to log Kow ≥4, and use of a single test concentration. The resulting reduction in the use of fish is consistent with the 3 R s principle and did not adversely affect classification accuracy. An assessment of potential risk of secondary poisoning was also conducted for three drugs classified as either B or vB, and no risks were identified.

项与依塞曲匹相关的新闻（医药）

2024-07-30

·药融圈

多家大药厂折戟，成功率0%高难度靶点，荷兰小型biotech能否率先破局？

▲8月15-16日苏州2024生物医药创新者峰会扫码报名注：本文不构成任何投资意见和建议，以官方/公司公告为准；本文仅作医疗健康相关药物介绍，非治疗方案推荐（若涉及），不代表平台立场。任何文章转载需得到授权。心血管疾病是全球的主要死亡原因，根据药融咨询《中国心血管系统药物分析报告》，近30年，全球心血管疾病（CVD）患病人数几乎翻了一番，从1990年的2.7亿例增长到2019年的5.23亿例，人口增长和老龄化是心血管疾病患病人数增长的主要驱动因素。其中，动脉粥样硬化是心脏病发作、中风和周围血管疾病的主要原因，动脉粥样硬化性心血管疾病（ASCVD）最重要的危险因素之一是高胆固醇血症，即体内LDL-C（低密度脂蛋白胆固醇）水平升高。他汀类药物是一类降脂药物，是目前治疗高危心血管病伴高胆固醇患者的标准治疗药物，然而，相当比例的高胆固醇患者单独使用他汀类药物治疗不能将LDL-C降至理想水平。虽然目前市场上有非他汀类药物治疗方案，例如PCSK9（前蛋白转化酶枯草溶菌素9）抑制剂作为降脂治疗的新选择，但其价格昂贵且为注射制剂，限制广泛使用。因此，鉴于庞大的疾病人群，对于强效、经济和方便的低密度脂蛋白降低疗法作为他汀类药物的辅助治疗方面，依然存在着巨大的未满足需求。药融云数据www.pharnexcloud.com显示，NewAmsterdam Pharma（NASDAQ：NAMS，以下简称NAP）是一家总部位于荷兰纳尔登的临床阶段生物制药公司，其使命是改善代谢性疾病患者的治疗，这些疾病目前批准的疗法尚未足够成功或耐受不良。 NAP正在研究Obicetrapib，一种口服、低剂量和每日一次的CETP（胆固醇酯转运蛋白）抑制剂，作为首选的LDL-C（低密度脂蛋白胆固醇）降低疗法，用于高危心血管疾病患者的最大耐受剂量他汀类药物治疗的辅助治疗。同时，该公司认为CETP抑制有可能通过降低阿尔茨海默氏症、2型糖尿病等疾病的进展风险，从而在其他适应症中发挥作用。成功率0%的高难度靶点 CETP（胆固醇酯转运蛋白）是一种由肝脏分泌的血浆糖蛋白，介导胆固醇酯和甘油三酯在高密度脂蛋白（HDL）、极低密度脂蛋白（VLDL）和低密度脂蛋白（LDL）颗粒之间的双向转运。1980年代中期，日本首次报道了CETP（胆固醇酯转运蛋白）活性遗传缺陷及其与改善脂质成分（降低LDL-C和增加HDL-C），减少早发性动脉粥样硬化的关系。其实针对CETP（胆固醇酯转运蛋白）抑制剂，早已有几家大药厂开展过大规模研究，CETP曾被认为是心血管领域新的重磅靶点，但是针对这一靶点，依然没有药物上市，可见其开发难度之高。最先开启3期临床研究的CETP抑制剂是辉瑞的torcetrapib，但研究显示该药物增加了心血管事件和死亡的风险，最终不得不提前终止开发，而辉瑞已在该药物研发上斥资了8亿美元，torcetrapib成为了辉瑞研发史上最惨痛的失败之一。后来发现torcetrapib具有结构相关的脱靶效应，导致血压升高，醛固酮、类固醇和内皮素-1水平升高，以及电解质异常。有了前车之鉴，后来进入临床的几款CETP抑制剂均没有显示出脱靶效应特征，且具有良好的安全性，然而却因为没有达到预期疗效而终止了研究，包括罗氏的dalcetrapib（引进自日本烟草）和礼来的evacetrapib。2017年10月，默沙东宣布将不再寻求其CETP抑制剂anacetrapib的监管批准，理由是该药物的临床研究结果不支持上市申请，在3期研究中，anacetrapib仅使心脏病发作及死亡风险降低9%，同时，该药物会在脂肪组织中积聚，这使得商业化前景更不明朗。同一年，安进也宣布停止其CETP抑制剂AMG 899（Obicetrapib）的内部开发，并寻求对外许可机会，业界推测极大可能是受到了默沙东放弃递交anacetrapib上市申请的影响。曾经的最后一个CETP抑制剂并未退场安进的AMG 899（Obicetrapib）前称为TA-8995，由安进在2015年以15.5亿美元收购荷兰生物技术公司Dezima Pharma而得。根据药融云数据www.pharnexcloud.com提供线索，TA-8995由日本田边三菱制药株式会社（MTPC）最早进行研发，后授权给了Dezima Pharma，MTPC则保留了在亚洲某些地区（包括日本）的开发和商业化权利。截图自药融云数据库而本文的主角NewAmsterdam Pharma（以下简称NAP）在2020年从安进手中重新收购了Dezima Pharma，获得了Obicetrapib。NAP由荷兰阿姆斯特丹大学学术医学中心血管医学系的名誉医学教授John Kastelein博士和风险投资公司Forbion于2019年创立。而Dezima Pharma也是由John Kastelein教授于2012年创立，并受到了Forbion的资助。当2017年安进宣布停止Obicetrapib的内部开发并寻求对外许可之时，Forbion认为这种药物可以解决非常大的未满足医疗需求，并开始与安进公司对话，以继续开发该资产。为此Forbion与John Kastelein教授联合成立了NAP，目前Kastelein教授担任该公司的首席科学官。 2021年1月，NAP完成了1.96亿美元（1.6亿欧元）的A轮融资，由Forbion、Morningside Ventures和Ascendant BioCapital领投。从而支持Obicetrapib的3期临床开发。（相关阅读：1.96亿美元A轮融资，用于CETP抑制剂III期临床） 2022年6月，NAP与意大利制药公司美纳里尼集团签订了Obicetrapib在欧洲商业化的独家许可协议，同时保留在世界其他地区商业化Obicetrapib的所有权利（如果获得批准），以及开发某些形式的Obicetrapib用于治疗其他疾病（如阿尔茨海默病）的权利。（相关阅读：首付超1.4亿欧元，美纳里尼斩获心血管疾病新药obicetrapib） 2022年7月，NAP宣布与特殊目的收购公司Frazier Lifesciences Acquisition Corporation达成合并协议，合并后的新公司在纳斯达克上市，股票代码为“NAMS”。研究重点的转变最初在开发用于降低ASCVD（动脉粥样硬化性心血管疾病）风险的CETP抑制剂时，大家关注的重点在于其提高HDL-C（高密度脂蛋白胆固醇，俗称“好胆固醇”）的能力，但是现在CETP抑制剂的开发重点已确定为降低LDL-C（低密度脂蛋白胆固醇，俗称“坏胆固醇”）、非HDL-C和ApoB（载脂蛋白B）的能力，并受到了动物模型、观察性队列、孟德尔随机化研究、随机对照试验和大型荟萃分析等综合证据的支持。根据NAP披露，与先前的几款CETP抑制剂相比，Obicetrapib具有内在特性，如可电离特性，且亲脂性显著降低，因此该公司认为与其他CETP抑制剂相比，Obicetrapib作为候选药物具有更有利的物理、药代动力学和生物制药特性。将Obicetrapib与等效剂量的anacetrapib和evacetrapib相比，以及10mg剂量的Obicetrapib与100mg剂量的anacetrapib相比，Obicetrapib被证明可以更大程度地降低CETP活性。在NAP开展2b期ROSE试验中，在高强度他汀类药物的基础上，10 mg剂量Obicetrapib治疗显示LDL-C较基线降低51%；在2期ROSE2试验中，10 mg剂量Obicetrapib联合10 mg剂量依泽替米贝治疗显示LDL-C较基线降低了63%，研究达到了主要和次要终点。在评价Obicetrapib作为单药疗法或与10 mg依泽替米贝联用的5项2期临床研究（TULIP、ROSE、OCEAN、ROSE2以及在日本的2b期试验）中，均观察到LDL-C水平具有统计学意义的降低，其副作用的频率和严重程度与安慰剂相似。在NAP迄今开展的临床试验中，Obicetrapib在800多名血脂异常的患者中显示出良好耐受性。鉴于研究观察到的LDL-C降低能力和安全性，NAP选择10mg剂量的Obicetrapib开展3期临床研究，并设计了专门的心血管获益研究（CVOT），旨在避免以前CETP抑制剂研究方案的缺点，并期望最终能够满足那些尽管接受目前最佳降脂治疗但LDL-C水平仍然升高的ASCVD（动脉粥样硬化性心血管疾病）和/或HeFH（家族性高胆固醇血症）患者的未满足治疗需求。此外，NAP认为，Obicetrapib的口服递送、低剂量、化学特性和耐受性使其非常适合于联合治疗。该公司也正在开发Obicetrapib10 mg + 依泽替米贝10 mg的固定剂量组合。单药、联合疗法3期临床推进中目前，NAP围绕Obicetrapib作为单药疗法开展了2项关键3期临床试验，即BROADWAY和BROOKLYN，以评估Obicetrapib作为最大耐受剂量降脂疗法的辅助疗法，以潜在地进一步降低ASCVD或HeFH患者的LDL-C水平。这两项研究已在2023年完成入组，BROADWAY研究随机分配了超过2500名患者，BROOKLYN研究随机分配了超过350名患者。该公司预计将分别于2024年Q3和Q4公布BROOKLYN研究和BROADWAY研究的顶线数据。 2022年3月，NAP启动了3期CVOT（心血管获益）研究PREVAIL，旨在评估Obicetrapib减少MACE（主要心血管事件，包括心血管疾病死亡、非致死性心肌梗死、非致死性中风和非选择性冠状动脉重建术）发生率的潜力，该研究于2024年4月完成患者入组，随机分配了超过9500名患者，预计将于2026年公布顶线数据。对于联合疗法，NAP基于2期ROSE2临床试验的积极结果与经验，以及在2023年上半年完成的Obicetrapib 10 mg + 依泽替米贝10 mg固定剂量组合与原型药物的生物等效性实验，公司在2024年3月启动了关键3期临床试验TANDEM，以评估Obicetrapib 10 mg + 依泽替米贝10 mg固定剂量组合作为饮食控制和最大耐受剂量降脂疗法的辅助治疗，潜在地进一步降低HeFH、ASCVD或ASCVD高风险患者LDL（低密度脂蛋白）水平的能力。该研究计划在美国招募约400名基线LDL-C≥70 mg/dL的患者，预计将在2025年Q1公布顶线数据。NAP的目标是在递交Obicetrapib单药的NDA后不久，再递交一个固定剂量组合的NDA申请。 NAP计划在美国、欧盟、日本、中国和英国寻求Obicetrapib的批准。药融云数据www.pharnexcloud.com显示，Obicetrapib在国内正同步进行3期临床研究，主要临床机构为北京大学第一医院。截图自药融云数据库阿尔茨海默氏症、糖尿病的尝试 NAP认为，CETP抑制也可能通过潜在地降低诸如阿尔茨海默氏症或糖尿病等疾病的发展风险，在其他适应症中发挥作用。有证据表明，大脑中胆固醇的积累是阿尔茨海默氏病的前兆。例如，缺乏CETP基因的啮齿类动物对阿尔茨海默氏病有抵抗力。在早期的临床前研究中，当人类的CETP基因被敲入小鼠，小鼠大脑中的胆固醇含量增加了25%；当与淀粉样前体蛋白（假设是阿尔茨海默病的驱动因素）的基因结合时，在双转基因小鼠中观察到患类似阿尔茨海默病的疾病的风险大大增加。在一项临床前研究中，该公司观察到CETP抑制促进了大脑中胆固醇的清除并改善了认知能力。 NAP于2022年初开始了一项2a期开放标签和单臂试验，用于早期阿尔茨海默病和载脂蛋白E4（ApoE4）发生自然变异的患者，以评估Obicetrapib的药效学和药代动力学效应、安全性和耐受性，共13例患者给予Obicetrapib 10 mg，随访24周。2023年9月，该公司宣布了该试验初步数据，与基线水平相比，患者脑脊液中24-羟基胆固醇和27-羟基胆固醇的水平分别降低了11%和12%。此外，患者血浆中Aβ42/40比值较基线增加了8%，pTau181水平稳定。以往的CETP抑制曾在3期CVOT（心血管获益）研究中显示出抗糖尿病益处，若Obicetrapib也能显示出抗糖尿病益处，它将区别于目前的治疗方案，特别是与他汀类药物相比（他汀类药物可能致新发糖尿病的风险存在剂量依赖性）。NAP计划开展临床前研究以探索Obicetrapib治疗糖尿病患者的潜力，并已经将新发2型糖尿病作为Obicetrapib的3期CVOT研究PREVAIL的一个终点。财务状况 2023全年，NAP公司总收入为1410万美元，而上一年同期为1.027亿美元，这一下降主要是由于2022年收到了美纳里尼的预付款；2023年R&D费用为1.594亿美元，上一年同期为8670万美元，这一增长主要与正在进行的3期临床试验有关；SG&A费用为3760万美元，上一年同期为1950万美元，主要是因为公司人员增长。2023全年净亏损为1.769亿美元，或每股亏损2.15美元。 2024年Q1，NAP公司总收入为140万美元，而2023年同期为860万美元，这一下降主要是由于去年同期获得了临床相关里程碑收入；第一季度R&D费用为4240万美元，而2023年同期为4040万美元；SG&A费用为1450万美元，而2023年同期为810万美元，这一增长主要是由于团队扩张等，以支持Obicetrapib的商业化推出（若获得批准）。第一季度净亏损为9380万美元，或稀释后每股亏损1.06美元。 2024年2月，NAP宣布以1.753亿美元公开发行普通股和预融资认股权证，截至2024年3月31日，NAP拥有4.811亿美元的现金。截至7月4日，该公司市值约为18亿美元。截止发稿前市值为15.52亿美元，每股17.25美元。结语从田边三菱最早研发TA-8995（Obicetrapib）开始，这一分子在多年间几经转手，目前正处于关键3期临床研究阶段。今年6月，美国专利及商标局为Obicetrapib颁发了第三代物质组合物专利，该专利将Obicetrapib的知识产权保护和排他性延长至2043年7月。NewAmsterdam Pharma能否借助前面几家大厂的经验与教训将Obicetrapib推向成功？业内对CETP抑制剂的研发热情会重燃吗？我们可以拭目以待。此文仅用于向医疗卫生专业人士提供科学信息，不代表平台立场，不作任何用药推荐参考： NMPA/CDE；药融云数据www.pharnexcloud.com； FDA/EMA/PMDA；相关公司公开披露（正文图片均来自企业官方，除非另有说明）； https://www.newamsterdampharma.com/； Kastelein, John J P et al. “Obicetrapib: Reversing the Tide of CETP Inhibitor Disappointments.” Current atherosclerosis reports vol. 26,2 (2024): 35-44. doi:10.1007/s11883-023-01184-1； https://www.amgen.com/newsroom/press-releases/2015/09/amgen-to-acquire-privately-held-dezima-pharma； https://www.businesswire.com/news/home/20200825005160/en/NewAmsterdam-Pharma-Acquires-Obicetrapib-from-Amgen； https://www.prnasia.com/story/366920-1.shtml；等等 8月15日苏州国际博览中心C馆C102 新药创始人峰会会议日程 09:00-09:25 如何应对复杂的生物医药产业环境？（拟定，以会议现场为准）王兴利｜复星医药，执行总裁&创新药事业部联席CEO 09:25-09:50 跨越周期，承压下的中国Biotech公司还有哪些机会把握？（拟定，以会议现场为准）崔兴品｜华润医药集团，副总裁、华润三九医药董事 09:50-10:15 绕不开的商业化，Biotech公司该怎么看待商业化？（拟定，以会议现场为准）刘谦｜阿斯利康中国，副总裁 10:15-10:40 跨国公司视角：MNC在中国市场角色的转变 10:40-11:05 2024中国医药企业综合实力排行榜系列榜单发布杨建云｜药融云，副总经理 11:05-11:30 中国生物医药产业投资机会分析毛化｜沙利文，大中华区合伙人兼董事总经理 11:30-12:00 圆桌：中国Biotech公司未来突破点有哪些？ 1.被MNC并购，前提是准备好没？ 2.进入集采，创新药的想象力真的那么好？ 3.被国内大药企并购退出？ 4.抓住机会从Biotech到Biopharm? 5.以仿养创？怎么养？ 6.兼顾CRO业务获得现金流？卷得动吗？主持人：邓永奇｜凯复医药，CEO 王兴利｜复星医药，执行总裁&创新药事业部联席CEO 金方｜健康元，首席科学家刘谦｜阿斯利康中国，副总裁 12:00-13:30 午餐【中国新药的理性发展方向】论坛策划人&主持人：党群，真实生物，总裁 13:30-13:55 创新药是选FIC还是BIC？解决临床未满足需要是关键！党群｜真实生物，总裁 13:55-14:20 和誉医药FGFR抑制剂开发进展陈椎｜和誉医药，联合创始人兼CSO 14:20-14:45 细胞治疗产品动物药效评价曹保红｜美迪西，药理部副总裁 14:45-15:10 YAP/TEAD抑制剂的开发朱继东｜奕拓医药，CEO 15:10-15:35 浅谈“前药”的前世今生-长乘医药的前药研发宋钦辉｜长乘医药，CMO 15:35-16:00 慢乙肝功能性治愈创新药物的研究与开发张弛｜西安新通药物，副总经理 16:00-16:25 Delivery of Excellence - 递送引导的药物创新沈旺｜维眸生物，创始人、董事长兼CEO 扫码报名参会【关于药融圈】药融圈PRHub旨在帮助生物医药科技型企业进行品牌推广及商务拓展服务，针对客户的真实需求制定系统化解决方案，通过“翻译-降维-场景化”将客户的品牌信息以直白易懂的方式被公众知悉，同时在流量渠道覆盖100万+垂直用户基础上实现合作目的，帮助合作伙伴完成从品牌开始到商务为终的闭环营销服务。我们已经完成了数十场线下1000人规模的生物医药研发类会议，涵盖小分子新药，大分子新药，改良型新药，BD跨境交易等多个领域，服务了百余家上市/独角兽/生物技术/制药企业。

2023-11-17

·SYNAPSE

What are CETP inhibitors and how do you quickly get the latest development progress?

CETP, or Cholesteryl Ester Transfer Protein, plays a crucial role in lipid metabolism within the human body. It facilitates the transfer of cholesteryl esters (CE) and triglycerides (TG) between high-density lipoproteins (HDL) and low-density lipoproteins (LDL). By promoting the exchange of lipids, CETP contributes to the redistribution of cholesterol and triglycerides among lipoprotein particles. This process is essential for maintaining a healthy lipid profile and preventing the accumulation of cholesterol in the arteries. Understanding the function of CETP has led to the development of pharmaceutical interventions aimed at modulating its activity to improve cardiovascular health. Currently, the main drugs for increasing HDL-C include fibrates, niacin, and Cholesteryl Ester Transfer Protein (CETP) inhibitors. Among them, CETP inhibitors are the most potent in elevating HDL-C levels, making them a recent focus of major pharmaceutical companies. CETP is a plasma glycoprotein synthesized by the liver, most of which circulates in combination with HDL. The primary function of CETP is to mediate the transfer of cholesterol from HDL to VLDL and LDL during the process of triacylglycerol exchange, and CETP inhibitors can block this transfer process, theoretically possessing anti-atherosclerosis effects and the ability to reduce cardiovascular risks. The first CETP inhibitor developed by Pfizer in 2006, Torcetrapib, significantly increased HDL-C in coronary disease patients by 72.1%, but paradoxically, this increase led to a rise in cardiovascular events and mortality risk. In 2012, Dalcetrapib, a CETP inhibitor developed by Roche, significantly increased HDL-C levels by 31% to 40% compared to baseline in acute coronary syndrome patients during the dal-OUTCOMES phase III trial with an average follow-up of 31 months. However, the benefits in the primary endpoint (a composite of coronary death, nonfatal myocardial infarction, ischemic stroke, unstable angina, or cardiac arrest revival) were no better than the placebo group, and its development was also terminated. Lilly ceased development of its CETP inhibitor evacetrapib on October 12, 2015, and the prospects for Merck's anacetrapib are similarly bleak. However, research and development of CETP inhibitors have not stopped, with drugs such as BAY60-5521, JNJ-28545595, TA8895, and CKD519 gradually entering the preclinical development phase. Recent studies regarding the safety, tolerability, and pharmacodynamics of CKD-519 in a single ascending dose study with 40 healthy volunteers demonstrated that a single dose of CKD-519 (25 mg to 400 mg) significantly increased HDL-C levels without causing severe adverse events, nor causing an increase in blood pressure similar to that caused by Torcetrapib. Therefore, the issue that increasing HDL-C does not decrease cardiovascular events and mortality risk, as well as the future research direction for CETP inhibitors, have become recent points of discussion and research focus. How do they work?CETP inhibitors are a type of drug that target the cholesteryl ester transfer protein (CETP). CETP is a protein involved in the transfer of cholesterol esters between lipoproteins, such as high-density lipoprotein (HDL) and low-density lipoprotein (LDL). From a biomedical perspective, CETP inhibitors are designed to block the activity of CETP, thereby increasing the levels of HDL cholesterol and reducing the levels of LDL cholesterol. This mechanism is based on the understanding that higher levels of HDL cholesterol are associated with a lower risk of cardiovascular diseases, while elevated levels of LDL cholesterol are linked to an increased risk. By inhibiting CETP, these drugs aim to promote a favorable lipid profile and potentially reduce the risk of conditions like atherosclerosis, heart attacks, and strokes. However, it is important to note that the clinical efficacy and safety of CETP inhibitors are still being evaluated, and more research is needed to fully understand their potential benefits and risks. List of CETP InhibitorsThe currently marketed CETP inhibitors include: Ezetimibe/Pitavastatin CalciumDalcetrapibEvacetrapibObicetrapibObicetrapib/EzetimibeDRL-17822IcosabutateNST-1024CKD-508AnacetrapibFor more information, please click on the image below. What are CETP inhibitors used for?CETP inhibitors are approved indications include Hypercholesterolemia and Hyperlipoproteinemia Type II. For more information, please click on the image below to log in and search. How to obtain the latest development progress of CETP inhibitors?In the Synapse database, you can keep abreast of the latest research and development advances of CETP inhibitors anywhere and anytime, daily or weekly, through the "Set Alert" function. Click on the image below to embark on a brand new journey of drug discovery!

2023-09-17

·SYNAPSE

Nemesis of Hypercholesterolemia - CETP inhibitors

CETP, or Cholesteryl Ester Transfer Protein, plays a crucial role in lipid metabolism within the human body. It facilitates the transfer of cholesteryl esters (CE) and triglycerides (TG) between high-density lipoproteins (HDL) and low-density lipoproteins (LDL). By promoting the exchange of lipids, CETP contributes to the redistribution of cholesterol and triglycerides among lipoprotein particles. This process is essential for maintaining a healthy lipid profile and preventing the accumulation of cholesterol in the arteries. Understanding the function of CETP has led to the development of pharmaceutical interventions aimed at modulating its activity to improve cardiovascular health. CETP Competitive LandscapeAccording to the data provided by Patsnap Synapse-Global Drug Intelligence Database: the following figure shows that as of 10 Sep 2023, there are a total of 39 CETP drugs worldwide, from 46 organizations, covering 25 indications, and conducting 173 clinical trials. 👇Please click on the picture link below for free registration or login directly if you have freemium accounts, you can browse the latest research progress on drugs , indications, organizations, clinical trials, clinical results, and drug patents related to this target. The analysis of target CETP from various perspectives provides valuable insights into the current competitive landscape and future development. Kowa Co., Ltd., NewAmsterdam Pharma Co. NV, and DalCor Pharmaceuticals Canada, Inc. are among the companies with drugs in advanced phases. Hypercholesterolemia and Hyperlipoproteinemia Type II are the approved indications for target CETP drugs. Small molecule drugs dominate the development landscape, with intense competition indicated by the presence of biosimilars. Japan, the United States, and the European Union are leading in terms of development, with China also making progress. Overall, the target CETP shows promising potential for addressing various indications related to cardiovascular diseases and lipid metabolism disorders. CETP Inhibitor Entering Phase III Clinical Trials:ObicetrapibObicetrapib is a small molecule drug that falls under the category of biomedicine. It specifically targets CETP. The drug is primarily focused on treating various therapeutic areas including Endocrinology and Metabolic Disease, Nervous System Diseases, and Cardiovascular Diseases. Obicetrapib has been identified to be effective in treating several active indications. These include Heterozygous familial hypercholesterolemia, Atherosclerosis, Dyslipidemias, Hypercholesterolemia, Alzheimer Disease, and Hyperlipidemias. These indications highlight the drug's potential in managing cholesterol-related disorders and neurodegenerative conditions such as Alzheimer's disease. 👇Please click on the image below to directly access the latest data (R&D Status | Core Patent | Clinical Trial | Approval status in Global countries) of this drug. The originator organization responsible for the development of Obicetrapib is Mitsubishi Tanabe Pharma Corp. This pharmaceutical company has been actively involved in the research and development of this drug. In terms of clinical development, Obicetrapib has reached Phase 3 of clinical development globally. This indicates that the drug has undergone extensive preclinical testing and has progressed to advanced stages of clinical trials involving a larger patient population. Phase 3 trials are crucial in evaluating the drug's safety, efficacy, and dosage requirements before seeking regulatory approval. Similarly, in China, Obicetrapib has also reached Phase 3 of clinical development. This suggests that the drug's development has progressed to an advanced stage in the Chinese market as well. In summary, Obicetrapib is a small molecule drug developed by Mitsubishi Tanabe Pharma Corp. It targets CETP and shows potential in treating various therapeutic areas such as Endocrinology and Metabolic Disease, Nervous System Diseases, and Cardiovascular Diseases. The drug has active indications including Heterozygous familial hypercholesterolemia, Atherosclerosis, Dyslipidemias, Hypercholesterolemia, Alzheimer Disease, and Hyperlipidemias. With its highest phase being Phase 3 globally and in China, Obicetrapib has undergone extensive clinical development and is currently being evaluated for its safety and efficacy in larger patient populations. EvacetrapibEvacetrapib is a small molecule drug that is being developed to target CETP (Cholesteryl Ester Transfer Protein). It falls under the therapeutic areas of endocrinology and metabolic disease, specifically focusing on the treatment of hypercholesterolemia, which is characterized by high levels of cholesterol in the blood. The drug is being developed by Eli Lilly & Co., a renowned pharmaceutical company. 👇Please click on the image below to directly access the latest data (R&D Status | Core Patent | Clinical Trial | Approval status in Global countries) of this drug. As of the latest available information, Evacetrapib has reached Phase 3 of clinical development, on a global scale. Phase 3 trials are conducted to evaluate the safety and efficacy of a drug in a larger population, typically involving thousands of patients. This indicates that Evacetrapib has successfully progressed through earlier stages of development, including preclinical studies and Phase 1 and 2 trials. However, it is important to note that the highest phase of development for Evacetrapib in China is listed as "discontinued." This suggests that the drug's development in China has been halted or terminated at some point, possibly due to various reasons such as lack of efficacy, safety concerns, or strategic decisions by the originator organization. In summary, Evacetrapib is a small molecule drug developed by Eli Lilly & Co. that targets CETP and is intended for the treatment of hypercholesterolemia. It has reached Phase 3 of clinical development globally, indicating promising progress in its development. However, in China, the drug's development has been discontinued, suggesting potential challenges or setbacks specific to the Chinese market.

100 项与依塞曲匹相关的药物交易

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KEGG	Wiki	ATC	Drug Bank
D10121	依塞曲匹	-	DB11655

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
原发性高胆固醇血症	临床3期	日本	Eli Lilly & Co.	2014-11-01
高胆固醇血症	临床3期	美国	Eli Lilly & Co.	2014-10-01
高胆固醇血症	临床3期	波多黎各	Eli Lilly & Co.	2014-10-01
原发性高脂血症	临床3期	美国	Eli Lilly & Co.	2014-10-01
原发性高脂血症	临床3期	波多黎各	Eli Lilly & Co.	2014-10-01
血管疾病	临床3期	美国	Eli Lilly & Co.	2012-10-01
血管疾病	临床3期	中国	Eli Lilly & Co.	2012-10-01
血管疾病	临床3期	日本	Eli Lilly & Co.	2012-10-01
血管疾病	临床3期	阿根廷	Eli Lilly & Co.	2012-10-01
血管疾病	临床3期	澳大利亚	Eli Lilly & Co.	2012-10-01

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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


NCT01537887 (CTgov)	临床1期	-	72	Placebo	糧遞製鑰憲遞鹹衊醖醖(夢鹽製鹽遞襯窪襯顧艱) = 選糧簾鹹鬱構窪艱糧鹽糧遞簾製獵觸鏇積壓淵 (壓鏇鬱廠觸窪願鬱築壓, 7.5) 更多	-	2019-03-07
NCT02271425 (CTgov)	临床1期	-	8	Evacetrapib Tablet	選廠淵範廠簾憲網獵繭(齋積築選遞網範獵醖齋) = 遞壓願齋窪製夢鹽範襯觸鏇鹽願憲鬱餘遞網餘 (艱夢襯餘窪獵觸簾窪糧, 糧遞艱範鑰觸夢網齋壓 ~ 憲願襯齋憲遞簾壓築膚) 更多	-	2019-03-01
NCT02497391 (CTgov)	临床1期	-	95	Evacetrapib (Evacetrapib Reference (R))	襯蓋積餘蓋築築淵鏇襯(顧蓋窪膚簾鬱繭獵鹽網) = 憲鏇鏇憲簾顧窪觸築積鏇餘鬱網壓範鹹窪鹽網 (選範積範鬱網襯簾鏇繭, 78) 更多	-	2018-12-03
				Evacetrapib (Evacetrapib Test 1 (T1))	襯蓋積餘蓋築築淵鏇襯(顧蓋窪膚簾鬱繭獵鹽網) = 艱觸壓範範衊艱網獵鹽鏇餘鬱網壓範鹹窪鹽網 (選範積範鬱網襯簾鏇繭, 56) 更多
NCT01375075 (CTgov)	临床2期	血脂障碍	165	Placebo+LY2484595 (100 mg LY2484595)	積構鑰廠鏇鬱膚鹹艱積(鏇遞築壓醖壓鑰餘醖鏇) = 憲醖醖鹹廠鑰膚鹹廠餘襯夢積鏇鹹築壓觸構壓 (願遞遞蓋鏇夢鏇顧憲鑰, 8.92) 更多	-	2018-10-25
				Placebo+LY2484595 (500 mg LY2484595)	積構鑰廠鏇鬱膚鹹艱積(鏇遞築壓醖壓鑰餘醖鏇) = 襯醖餘獵網壓窪觸壓鑰襯夢積鏇鹹築壓觸構壓 (願遞遞蓋鏇夢鏇顧憲鑰, 9.16) 更多
NCT01836185 (CTgov)	临床1期	肝功能不全	32	Evacetrapib (Evacetrapib (Healthy))	網衊齋鹽範襯膚觸鑰鬱(鏇齋顧網鬱觸壓選積鹽) = 壓顧鹹鬱窪衊壓積鏇積範糧壓夢窪糧醖憲鹽憲 (遞積選膚願範築窪鏇襯, 50) 更多	-	2018-10-12
				Evacetrapib (Evacetrapib (Hepatic, Mild))	網衊齋鹽範襯膚觸鑰鬱(鏇齋顧網鬱觸壓選積鹽) = 襯獵窪鹹壓鑰簾鏇鹹鬱範糧壓夢窪糧醖憲鹽憲 (遞積選膚願範築窪鏇襯, 84) 更多
NCT01810432 (CTgov)	临床1期	-	40	Evacetrapib (Evacetrapib (Fasted))	遞蓋壓鏇遞餘糧積壓範(廠遞夢範艱築蓋鬱範鹽) = 積膚襯獵獵遞積鬱積網鹽選繭觸醖製觸願壓構 (鑰鑰糧鹹膚糧積窪鬱願, 73) 更多	-	2018-10-12
				High-fat Meal+Evacetrapib (Evacetrapib (Fed))	遞蓋壓鏇遞餘糧積壓範(廠遞夢範艱築蓋鬱範鹽) = 醖糧網糧餘願膚憲餘鹽鹽選繭觸醖製觸願壓構 (鑰鑰糧鹹膚糧積窪鬱願, 22) 更多
NCT02226653 (CTgov)	临床1期	-	48	evacetrapib (Reference (Fasted))	糧淵鹹願選襯餘簾廠淵(範糧鹹鬱鹹鑰遞衊積夢) = 齋觸鑰顧夢餘築遞繭醖廠蓋鹽廠齋糧窪網鏇糧 (築鬱衊衊鬱鑰壓壓網築, 40) 更多	-	2018-10-10
				evacetrapib (Test (Fasted))	糧淵鹹願選襯餘簾廠淵(範糧鹹鬱鹹鑰遞衊積夢) = 製鏇淵簾遞襯觸淵築鑰廠蓋鹽廠齋糧窪網鏇糧 (築鬱衊衊鬱鑰壓壓網築, 36) 更多
NCT02260648 (CTgov)	临床3期	原发性高胆固醇血症	149	Evacetrapib+Atorvastatin (Evacetrapib)	衊築憲憲網顧醖構範夢(鏇網簾鑰廠遞選糧鹽蓋) = 簾窪餘鹹鑰範鑰醖範選糧糧鬱網積鏇鬱觸齋艱 (鏇願鬱齋鏇遞夢夢蓋窪, 3.108) 更多	-	2018-10-09
				Placebo+Atorvastatin (Placebo)	衊築憲憲網顧醖構範夢(鏇網簾鑰廠遞選糧鹽蓋) = 鬱願膚選觸鏇鑰壓齋構糧糧鬱網積鏇鬱觸齋艱 (鏇願鬱齋鏇遞夢夢蓋窪, 3.264) 更多
NCT01897493 (CTgov)	临床1期	-	16	Digoxin (Digoxin)	壓艱憲憲簾鑰醖窪積鏇(鏇鏇鏇艱積餘憲鑰構鏇) = 壓餘鏇觸築繭鬱選襯顧簾積膚製築製淵夢夢衊 (窪鏇窪衊艱範構繭獵構, 襯窪鹹選簾淵夢鑰範簾 ~ 窪範獵壓築遞衊選夢醖) 更多	-	2018-10-09
				Evacetrapib+Digoxin (Evacetrapib + Digoxin)	壓艱憲憲簾鑰醖窪積鏇(鏇鏇鏇艱積餘憲鑰構鏇) = 齋構夢構觸構廠糧簾積簾積膚製築製淵夢夢衊 (窪鏇窪衊艱範構繭獵構, 選選艱網衊顧鬱鑰膚壓 ~ 膚夢壓選鏇醖襯窪鏇構) 更多
NCT01825876 (CTgov)	临床1期	血栓形成	17	Warfarin (Warfarin)	繭觸蓋構顧衊獵網繭膚(餘鹹範鏇淵積窪願鏇顧) = 淵鬱糧築選築觸簾衊廠膚壓顧顧顧構鬱鬱積範 (顧淵繭選艱築餘範鹹選, 35)	-	2018-10-09
				Evacetrapib+Warfarin (Evacetrapib + Warfarin)	繭觸蓋構顧衊獵網繭膚(餘鹹範鏇淵積窪願鏇顧) = 繭觸觸衊願窪鏇襯壓壓膚壓顧顧顧構鬱鬱積範 (顧淵繭選艱築餘範鹹選, 39)