A Phase III, Randomised, Double-blind, Placebo-controlled, Parallel-group Study to Assess the Effect of AZD0780 on Major Adverse Cardiovascular Events in Patients With Established Atherosclerotic Cardiovascular Disease (ASCVD) or at High Risk for a First ASCVD Event

The purpose of this phase 3, randomized, placebo controlled, event-driven study is to assess the effect of AZD0780, an oral PCSK9 inhibitor, compared with placebo in reducing the risk of MACE-PLUS in patients with established ASCVD or at high risk for a first ASCVD event. The effect of AZD0780 vs placebo on the risk of MACE-PLUS will be evaluated from randomisation until the primary analysis censoring date (PACD). The Study Closure Visit will be scheduled to occur after the PACD and will be the final visit for each participant in the study.

开始日期2025-06-06

申办/合作机构

AstraZeneca PLC

NCT07000123

/ Not yet recruiting临床3期

A Phase III, Randomised, Double-Blind, Placebo-Controlled, Parallel-Group Study to Assess the Effect of AZD0780 on Low-Density Lipoprotein Cholesterol in Patients With Elevated Low Density Lipoprotein Cholesterol and Clinical Atherosclerotic Cardiovascular Disease or at Risk for a First Atherosclerotic Cardiovascular Disease Event

This is a study to evaluate the efficacy and safety of AZD0780 in adults with clinical ASCVD or who are at risk for a first ASCVD event and who have elevated LDL-C. AZD0780 is a small molecule that reduces the amount of LDL-C in the blood. Placebo will be used for comparison, and neither the participants nor the Investigators will know who is receiving the AZD0780 medication and who is receiving the placebo until the end of study.
The total length of the study for an individual participant will be up to approximately 56 weeks, including a screening period of up to 14 days, treatment with AZD0780 or placebo for 52 weeks, and a safety follow-up period of 10 days.

开始日期2025-05-30

申办/合作机构

AstraZeneca PLC

NCT07000136

/ Not yet recruiting临床3期

A Phase III, Randomised, Double-Blind, Placebo-Controlled, Parallel-Group Study to Assess the Effect of AZD0780 on Low-Density Lipoprotein Cholesterol in Patients With Heterozygous Familial Hypercholesterolaemia

This is a study to evaluate the efficacy and safety of AZD0780 in adults with HeFH and elevated LDL-C, either with clinical ASCVD and LDL-C levels of 55 mg/dL or higher or without clinical ASCVD and LDL-C levels of 70 mg/dL or higher. AZD0780 is a small molecule that reduces the amount of LDL-C in the blood. Placebo will be used for comparison, and neither the participants nor the Investigators will know who is receiving the AZD0780 medication and who is receiving the placebo until the end of study.
The total length of the study for an individual participant will be up to approximately 56 weeks, including a screening period of up to 14 days, treatment with AZD0780 or placebo for 52 weeks, and a safety follow-up period of 10 days.

开始日期2025-05-30

申办/合作机构

AstraZeneca PLC

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项与 Laroprovstat 相关的文献（医药）

2025-12-01·Current Atherosclerosis Reports

Oral PCSK9 Inhibitors: Will They Work?

Review

作者: Catapano, Alberico L ; Pirillo, Angela ; Tokgözoğlu, Lale

PURPOSE OF REVIEW:

Lowering low-density lipoprotein cholesterol (LDL-C) is a crucial step in reducing the risk of atherosclerotic cardiovascular disease. Inhibitors of proprotein convertase subtilisin/kexin type 9 (PCSK9), an important regulator of circulating LDL-C levels, represent a modern approach for the treatment of hypercholesterolaemia. Approved approaches targeting PCSK9 to date include injectable biologics. Here, we provide an overview of the current state of research on the development of oral PCSK9 inhibitors.

RECENT FINDINGS:

Several small molecules have been developed in recent years. Enlicitide decanoate (formerly known as MK-0616) has been shown to significantly reduce LDL-C levels by a maximum of 66% from baseline with a good safety and tolerability profile. Its formulation with sodium caprate enabled a higher bioavailability. Several clinical trials are currently underway to evaluate the efficacy and safety of this drug, including an outcome trial. AZD0780 is another oral small molecule that lowers LDL-C levels by 52% and can be administered on top of a statin. Several other small molecules with the potential to inhibit PCSK9 have been identified, some of which have stopped the development. Oral PCSK9 inhibitors are showing promising results in early studies. If the results of the outcome studies will be positive, we will have a safe, effective and easy-to-use oral therapy. Oral PCSK9 inhibitors could provide a convenient alternative to injectable PCSK9 inhibitors and result in a greater number of patients receiving an effective LDL-C-lowering therapy.

2025-06-01·JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY

An Oral PCSK9 Inhibitor for Treatment of Hypercholesterolemia

Article

作者: Yu, Hongtao ; Xu, Yuejia ; Twaddle, Lee ; Middlemiss, Jessica ; Agrawal, Nikhil ; McCarthy, Michael C ; Wallerstedt, Emelie ; Barbour, April M ; Carter, Debra ; Koren, Michael J ; Vega, Rick B ; Rosenmeier, Jaya B

BACKGROUND:

Most patients at high-risk for cardiovascular events do not achieve lipid goals advocated by American College of Cardiology/American Heart Association (ACC/AHA) guidelines despite the wide availability of lipid-lowering therapy. AZD0780 is a novel, oral, small molecule inhibitor of proprotein convertase subtilisin/kexin type 9 (PCSK9) in development as a once-daily treatment for hypercholesterolemia.

OBJECTIVES:

The phase 2 randomized, double-blind, placebo-controlled, multicenter PURSUIT trial evaluated the efficacy and safety of AZD0780 in patients with hypercholesterolemia already on background moderate-to-high-intensity statin treatment.

METHODS:

Eligible study patients had a fasting low-density lipoprotein cholesterol (LDL-C) level of ≥70 mg/dL (1.8 mmol/L) and <190 mg/dL (4.9 mmol/L), and triglycerides <400 mg/dL on stable dose of moderate- or high-intensity statins, as defined by ACC/AHA or local guidelines, with or without ezetimibe at baseline. The study randomized patients 1:1:1:1:1 to receive AZD0780 1, 3, 10, or 30 mg, or matching placebo, oral once daily, for 12 weeks. The primary efficacy endpoint was percent change of LDL-C from baseline to week 12. Safety and tolerability evaluations included the number of adverse events, vital signs, electrocardiograms, and laboratory assessments.

RESULTS:

In total, the study randomized 428 patients, of whom 426 started treatment. Patients were 52.1% male, with an average age of 62.4 ± 7.6 years. At week 12, compared with baseline, the placebo-corrected difference in least squares mean percent change of LDL-C for AZD0780 1, 3, 10, and 30 mg vs placebo was -35.3% (95% CI: -43.6% to -26.9%), -37.9% (95% CI:-46.3% to -29.5%), -45.2% (95% CI: -53.5% to -36.9%), and -50.7% (95% CI: -59.0% to -42.4%), respectively. Baseline statin use, moderate vs high intensity, did not alter AZD0780 efficacy. The proportion of patients reaching the ACC/AHA guideline LDL-C goal for high-risk patients increased in a dose-proportional manner. Adverse events compared similarly between the total AZD0780 treatment group (38.2%) and placebo (32.6%).

CONCLUSIONS:

AZD0780 demonstrated robust, dose-dependent reductions in LDL-C with a favorable safety and tolerability profile supporting further development of this once daily, oral treatment. (A Study to Assess the Efficacy, Safety and Tolerability of Different Doses of AZD0780 in Patients With Dyslipidemia [PURSUIT]; NCT06173570).

2025-03-01·Atherosclerosis plus

Emerging oral therapeutic strategies for inhibiting PCSK9

Review

作者: Marodin, Giorgia ; Ferri, Nicola

Pharmacological inhibition of Proprotein Convertase Subtilisin/Kexin 9 (PCSK9) have been firmly established to be an effective approach to reduce low-density lipoprotein (LDL) cholesterol levels and cardiovascular events. Subcutaneous administration of monoclonal antibodies (evolocumab and alirocumab) every 2 or 4 weeks determined a 60 % reduction of LDL cholesterol levels, while the GalNac-siRNA anti PCSK9 (inclisiran) provided an effective lipid lowering activity (-50 %) after an initial subcutaneous dose, repeated after 3 months and followed by a maintenance dose every 6 months. Although these two approaches have the potentiality to bring the majority of patients at high and very-high cardiovascular risk to the appropriate LDL cholesterol targets, their cost and subcutaneous administration represent a strong limitation for their large-scale use. These problems could be overcome by the development of small chemical molecules anti PCSK9 as oral therapy for controlling hypercholesterolemia. In the present review, we summarized the pharmacological properties of oral anti PCSK9 molecules that are currently under clinical development (DC371739, CVI-LM001, and AZD0780), including the mimetic peptides enlicitide decanoate (MK-0616) and NNC0385-0434.

项与 Laroprovstat 相关的新闻（医药）

2025-05-15

·阿基米德Biotech

千亿市场，鲶鱼来袭

CVM（心血管及代谢），此词重量将堪比ADC、GLP-1。国内心血管疾病患者约3.3亿人、代谢性疾病患者约4.5亿人。据药融云，2018-2022年，中国心血管药物销售额市场规模保持在1450亿元左右。然而，这个超级市场一潭死水，长期被MNC和仿制药企盘踞。死水微澜，创新例外，国内创新药唯一接近百亿大单品，有望诞生于CVM，验证结构性增量逻辑成立。创新靶点成药，以及创新靶点进一步开发小分子药（口服优势）、小核酸药（超长效），让增量Buff拉满。Biotech在站稳肿瘤领域后，正挟创新靶点集体进军CVM。CVM市场将分层，保底层是集采仿制药，量大管饱，承担普惠的社会责任，中间层是口服创新药和次新靶点单抗药或多肽药，顶层是高价值的小核酸药、基因编辑疗法和全新靶点单抗药或多肽药。拿下中间层和顶层，Biotech将改变命运，享受慢病用药品牌依赖度高、生命周期长的红利。散发着腐烂气息的千亿江湖，因为鲶鱼涌入而重生。2023年主要降脂药品种价格梳理，初步呈现价格分层资料来源：新康界，赛柏蓝，药智网，各药品说明书，华福证券研究所01 MNC凭老药霸屏依旧，仿制药拼老命只赚吆喝国内CVM慢病用药，曾经几乎被MNC垄断。据米内网，2021年中国城市实体药店终端降压药TOP10品牌市场份额、降糖药TOP10品牌市场份额、降脂药TOP10品牌市场份额，外企分别占9席、9席、6席。集采让原研药出局，打破药品阶层板结化？据米内网，2024年Q1-Q3重点省市公立医院终端高血压用药市场品牌TOP20中，外企占据15席；2024年中国零售药店终端糖尿病用药（化+生）品牌TOP20中，外企占据17席；2024年Q1-Q3中国零售药店终端内服血脂调节剂品牌TOP20中，外企占据7席。降压药、降糖药原研霸屏依旧，原研崇拜本质上是一种品牌依赖，客户粘度高，服用周期长，不会轻易中途换药。降脂药市场格局表面上受到国产集采品种的强劲冲击。据药智数据，阿托伐他汀钙片作为首批国家集采的血脂调节药大品种，在执行中标结果前的最后一个完整年度（2018年），在国内公立医疗机构的销售量为16.08亿片，辉瑞原研药为8.87亿片，占比55%，到2023年，阿托伐他汀钙片已增长至30.46亿片，辉瑞原研药为8.51亿片，占比降至28%。齐鲁制药勇夺阿托伐他汀钙片市场销量第一，销量占比47%，紧随其后的是乐普制药和东瑞制药（原兴安药业），销量占比分别为10%和9%。一看销售额，结局就反转。阿托伐他汀钙片2018年国内公立医疗机构销售额为105.01亿元，其中，辉瑞原研药占市场份额71%，集采之后，辉瑞市场份额不降反升，2023年达到83%。国产负责管饱，进口负责赚钱？然而，一旦涉及集采，终究没有赢家。CVM大品种被集采暴击，阿托伐他汀钙片销售额由2018年超100亿下滑至2020年不足55亿元；瑞舒伐他汀钙片由2018年超60亿元下滑至2021年不足25亿元；苯磺酸氨氯地平片由2018年近50亿元下滑至2020年不足23亿元。在CVM未被集采的领域，一个接近百亿元的大单品正冉冉升起。阿斯利康当家花旦达格列净（SGLT-2抑制剂），身披未被集采+原研战袍，据米内网，2024H1在国内三大终端六大市场的销售额接近35亿元，同比增长39.16%，按此趋势（据阿斯利康财报，达格列净全球销售额2024年同比增长31%，2025Q1同比增长16%），2025年或2026年将接近100亿元。达格列净被视为新型降糖药，其实不太新了，最早于2012年11月在欧洲批准上市，2017年3月在中国获批上市，到2022年，达格列净仍然占据国内SGLT-2药物82.6%的市场份额。整个CVM药物迭代缓慢。即使上市近30年，即使是被集采按在地上摩擦，他汀类药物仍是血脂异常治疗基石，据药智数据，2024年前三季度的样本医院血脂调节剂化药销售额中，阿托伐他汀钙片和瑞舒伐他汀钙片的占比超过50%。这一潭死水，体现为药物迭代缓慢，MNC凭借原研老药霸屏依旧，仿制药拼了老命只赚一个吆喝。是时候，来一群鲶鱼了。这群鲶鱼正是迅速崛起的创新药企。创新药大本营在港股，而港股跟踪创新药最权威的指数是HSHKBIO，恒生医药ETF（159892）是HSHKBIO指数下规模最大的ETF，最新规模达到约47亿元。今年以来（截至5月14日），HSHKBIO累计上涨26.35%，跑赢同期恒生科技指数。随着源头创新、差异化创新能力的增强，创新药是未来中国投资主线之一，不要错过这一历史机遇。由于对专业知识要求太高，港股医药投资，最稳妥的选择还是ETF基金（159892恒生医药ETF）。这只基金也有对应的场外基金(A类：016970；C类：016971)，费率在同类属于最低档水平，可供长期定投。02 国产创新靶点药物，冲击三大旧格局仿制药未竟的任务，将由国产创新药完成。如果非要给恒瑞医药的创新转型找一个拐点标志，当属2025年3月将Lp (a)口服小分子项目HRS-5346海外权益许可给默沙东，首付款2亿美元，交易总额19.7亿美元。这次BD令人全然耳目一新，不仅含新量远超恒瑞既往BD，而且在整个国产创新药出海事件中都属顶级水平，体现出恒瑞早研能力的巨大飞跃。这次BD不是发生于我们擅长的工程抗体领域，而是长期落后的CVM领域，更加意义非凡。对标海外大厂阿斯利康、罗氏的CVRM（心血管、肾脏及代谢疾病）业务线，信达生物搭建CVM领域全方位能力体系：降脂管线首个国产PCSK9单抗新进入国家医保目录生效；代谢管线玛仕度肽（GLP-1R/GCGR）——全球首个进入III期GLP-1R/GCGR双靶点减重药，预计2025年中获批；痛风管线替古索司他（XO抑制剂）美国II期数据疗效优异，海外II期和国内II期同时推进；降压管线小核酸药物AGT siRNA国内I期已启动。CVM三大旧格局将经受国产创新靶点药物冲击。代谢领域，以信达生物玛仕度肽为代表的GLP-1药物即将汹涌而至，围绕GLP-1升级，以来凯医药LAE102（ActRIIA单抗）为代表的早研药物，在增肌、增加能量消耗、停药不反弹的痛点上进行探索；降压领域，中国约有2.6亿高血压患者，且高血压控制率较低，仅为16%，AGT是RAAS通路的上游靶点，RNA疗法可沉默肝源性AGT基因表达，有望克服RAS逃逸，解决高血压治疗耐药和依从性差的问题，半年给药一次，国产8款靶向AGT小核酸药物已进入临床，包括舶望制药 BW-00163、圣因生物/信达生物SGB-3908、石药集团SYH2062、恒瑞医药HRS-9563、成都先衍生物LDR2402、昂拓生物ART101、施能康/华东医药SNK-2726、大睿生物RN1871；限于篇幅，今天分析重点为新型降脂药。降脂领域仍存较大未满足需求。任何一种他汀类药物剂量倍增时，LDL⁃C（低密度脂蛋白胆固醇）进一步降低幅度仅约6%，此所谓“他汀类药物疗效6%效应，即LDL-C疗效不足；部分患者存在他汀不耐受的情况，包括肝功能异常、他汀类药物相关肌肉并发症、新发糖尿病以及其他不良反应；脂蛋白(a)也称Lp(a)，Lp(a)水平的增加与心血管疾病风险的增加直接相关，其浓度几乎完全由遗传决定，传统降脂药物（如他汀类）作用有限。全球靶向PCSK9药物在研情况梳理截至2025年2月PCSK9PCSK9蛋白与LDL-R直接结合，相较他汀类药物的间接作用，PCSK9抑制剂可以更精准地降低LDL-C水平，对他汀不耐受的血脂异常患者，或难治性高胆固醇血症患者，均有较好疗效，肝肾副作用也相对较小。PCSK9单抗可使LDL-C水平降低达50%~70%，每2周1次皮下注射，但“一辈子打针”的心理负担沉重，长期依从性不佳。安进依洛尤单抗（2015年上市）、赛诺菲/再生元阿利西尤单抗（2015年上市）2024年全球销售额分别为22.2亿美元、12.5亿美元，分别同比增长35.4%、14.7%，并没有成为超级爆款。PCSK9三个潜力方向或可期待。一是开发小核酸药物，诺华Leqvio是全球首款上市的siRNA降血脂药物，2024年全球销售额7.5亿美元，同比增长108.3%，能够强效持久降低LDL-C，长期达标率达80%，亚洲人群降幅高于PCSK9单抗，关键是一年仅需两针（第三个月加强针后）。阿斯利康反义寡核苷酸（ASO）AZD8233可显著降低PCSK9及LDL-C水平73%~79%，这是迄今为止报道的所有PCSK9靶向药物中可使LDL-C水平降低最高的药物。国内石药集团、悦康药业、瑞博生物、圣因生物均在开发PCSK9 siRNA。二是开发口服药物。默沙东MK-0616是全球首个口服PCSK9抑制剂，属于大环肽类药物，可阻断PCSK9蛋白和LDLR的结合，IIb期临床研究中30mg组降低LDL-C水平达60.9%，已推至临床III期。阿斯利康AZD0780是一种PCSK9小分子抑制剂，基于瑞舒伐他汀再用药，LDL-C水平下降52%（联用下降78%）。三是开发PCSK9基因编辑技术。通过CRISPR–Cas基因编辑技术可实现PCSK9的永久抑制，有望实现一次注射，终生降血脂。今年4月，信立泰从尧唐生物引进的靶向PCSK9碱基编辑药物YOLT-101临床试验申请获得受理。YOLT-101 IIT研究数据显示，4周时，高剂量组受试者LDL-C最高降幅近80%。Lp（a）Lp(a)作为降脂治疗的新靶点，全球暂无药物获批上市。在中国，约有20%人群的Lp(a)水平异常。目前全球约有13款用于降低Lp(a)水平的药物处于研发阶段，其中进展最快的3个项目均已进入III期临床试验，分别为ASO疗法诺华Pelacarsen，以及siRNA疗法安进Olpasiran、礼来Lepodisiran。今年3月，礼来长效siRNA疗法II期研究结果出炉，lepodisiran在最高剂量（400mg）下，使Lp(a)水平在治疗后60至180天期间平均降低93.9%，达到主要终点，其中一些患者的降低时间持续近1.5年。国内进展最快的为舶望制药siRNA药物BW-01，已进入II期临床。恒瑞医药、石药集团、信立泰、京新药业、靖因药业均在布局靶向Lp(a)药物。APOC3siRNA热门靶点之一，改善脂质紊乱的新途径，主要针对高甘油三酯血症及罕见疾病。瑞博生物RBD5044是全球第二个进入临床开发的APOC3 siRNA。Arrowhead Pharmaceuticals/维亚臻研发的APOC3 siRNA 药物Plozasiran（VSA001），2025年 3 月针对中国家族性乳糜微粒血症综合征（FCS）患者的 III 期临床试验获得积极顶线数据，成功达到主要疗效终点和所有关键次要终点。ANGPTL3主要针对他汀类药物无效的高甘油三酯血症和家族性混合型高脂血症，有望成为罕见遗传病患者的曙光，目前全球仅有一款药物获FDA批准上市。恒瑞医药SHR-1918是ANGPTL3靶向单抗药物，进入Ⅲ期临床。润佳医药/君实生物、Arrowhead Pharmaceuticals/维亚臻、诺华/舶望制药均在开发ANGPTL3 siRNA。CETP一度被视为心血管重要靶点，却成为MNC的坟场，辉瑞、罗氏、礼来和默沙东均受阻。现存在研药物仅4款，均为口服小分子，NewAmsterdam制药公司于2024年12月公布了ObicetrapibⅢ期BROADWAY试验的积极结果，或成为该靶点的破局者。在CVM创新靶点上，国内创新药与MNC不存在技术代差，部分甚至站在同一起跑线上。恒瑞医药、信达生物、信立泰已成为CVM领军企业，大量Biotech更是风起云涌，不仅分享国内千亿市场的增量机会，还将出现更多大型BD。

核酸药物抗体药物偶联物带量采购基因疗法

2025-04-14

·BioSpace

Verve’s Base Editor ‘Numerically Beats’ Other Cholesterol-Lowering Drugs

iStock, piyaphat50 In a Phase Ib trial, VERVE-102 showed it could lower bad cholesterol across doses, setting up an opt-in decision for Eli Lilly and a showdown with Novartis. Verve Therapeutics’ in vivo base editing therapy, VERVE-102, lowered bad cholesterol in Phase Ib, the company announced Monday morning, leaving the company’s partner, Eli Lilly, with a decision to make. Analysts from both William Blair and BMO Capital Markets pointed to the asset’s “clean” safety pro notes to investors Monday morning. Safety was the trial’s primary outcome. VERVE-102 targets and permanently shuts off the PCSK9 gene specifically in the liver, with the aim of reducing low-density lipoprotein cholesterol (LDL-C, so-called “bad” cholesterol) to treat heterozygous familial hypercholesterolemia (HeFH), where high cholesterol can lead to strokes and heart attacks. The therapy is part of a $60 million deal with Eli Lilly signed in 2023 , where the larger pharma can opt-in to take over development of the therapy after Phase I trials are completed. VERVE-102 showed dose-dependent reductions in LDL-C, with the lowest dose eliciting a 21% average reduction while the highest led to a 53% reduction, with one patient in the highest dose cohort seeing a 69% reduction. These data from the highest-dose cohort “numerically [beat] the LDL-C lowering bar for a long-acting PCSK9 inhibitor set by [Novartis’] Leqvio,” which elicited a 39.7% LDL-C lowering for HeFH patients, William Blair analysts said Monday. Verve could also differentiate itself from Leqvio in another way: VERVE-102 is a one-time therapy, while Leqvio is given twice per year. Verve reported “no treatment-related [serious adverse effects], no dose-limiting toxicities, and no cardiovascular events observed,” according to its press release. “We believe the absence of dose-dependent changes in [adverse effects] points to a wide VERVE-102 therapeutic index,” BMO wrote. VERVE-102’s continuing development sets it up for a showdown with Leqvio, an siRNA treatment that also targets PCSK9. Novartis licensed the drug from Alnylam in 2020, winning FDA approval in 2021 . The William Blair analysts also compared VERVE-102 to Merck’s investigational PCSK9 drug MK-0616, which has achieved similar LDL-C-lowering numbers, while noting that food consumption lowers its bioavailability . AstraZeneca also has a drug candidate in the running, AZD0780, though William Blair noted that daily dosing might be a disadvantage. Monday’s results may come as a relief to Verve. A year ago, the company halted development of a similar PCSK9 gene editor, VERVE-101, due to Grade 3 drug-induced thrombocytopenia. The company at the time attributed those abnormalities to the lipid nanoparticle delivery system used by VERVE-101. Verve then pivoted to VERVE-102, which uses a different nanoparticle. Two months ago, Vertex severed a $400 million agreement signed with Verve in 2022 to co-develop gene therapies together.

临床结果临床1期上市批准基因疗法

2025-04-09

·药明康德

年度十大“明星分子”榜单出炉

▎药明康德内容团队编辑编者按：近日，知名产业媒体猎药人（Drug Hunter）发布了2024年度明星分子榜单。从数以万计的研究论文中，猎药人依据技术创新、科学贡献、潜在临床价值以及独创性等多个维度，结合读者和评审专家的综合意见，最终选取十款明星分子入围榜单。经过读者投票，Vertex公司开发的“first-in-class”止痛药suzetrigine名列榜首。在这十大明星分子中，药明康德化学业务平台很高兴能为其中多款提供赋能服务，推动创新落地。未来，我们期待能进一步助力更多合作伙伴，加速创新疗法的研发，为全球病患提供更多治疗选择。Suzetrigine：口服NaV1.8离子通道抑制剂图片来源：猎药人官网Suzetrigine是Vertex Pharmaceuticals公司开发的“first-in-class”口服NaV1.8离子通道选择性抑制剂。电压门控钠离子通道是介导神经元释放动作电位的重要离子通道。人类遗传学研究显示，编码NaV1.8的基因的失活性突变让个体对疼痛不敏感，而功能获得性突变则会导致持续疼痛。Vertex的研究人员通过分析离子通道开关过程中快速发生的构象变化，发现了新的潜在结合位点。Suzetrigine对NaV1.8离子通道的选择性与其它NaV相比最终达到了3万到4万倍。Suzetrigine在今年1月获得美国FDA的批准（商品名Journavx），用于治疗成人中度至重度急性疼痛。Vertex公司的新闻稿指出，Journavx是20多年来首个获得FDA批准用于治疗急性疼痛的新机制药物。它有望在缓解患者疼痛的同时，减少与服用阿片类止痛药相关的潜在副作用和上瘾风险。Zoldonrasib（RMC-9805）：KRAS G12D突变体选择性共价抑制剂图片来源：猎药人官网RMC-9805是Revolution Medicines公司开发的KRAS G12D突变体选择性共价抑制剂。它基于该公司独有的三元复合体（Tri-Complex）抑制剂平台，与伴侣蛋白cyclophilin A结合后，可以与激活状态下的KRAS突变体以高亲和力形成三元复合体。RMC-9805同时能够与KRAS G12D突变体中第12位天冬氨酸形成交联，从而抑制KRAS G12D突变体的活性。去年10月，Revolution Medicines公布了RMC-9805的首个临床试验结果。在携带KRAS G12D突变的经治胰腺导管腺癌（PDAC）患者中，接受2期临床试验推荐剂量RMC-9805治疗患者的客观缓解率达30%，疾病控制率为80%。Daraxonrasib（RMC-6236）：非共价泛KRAS分子胶抑制剂图片来源：猎药人官网RMC-6236是Revolution Medicines公司开发的另一款泛KRAS抑制剂，同样利用了其三元复合体抑制剂平台，将cyclophilin A与激活状态下的KRAS突变体“粘合”在一起达到抑制KRAS活性的效果。去年12月公布的最新临床试验数据显示，在携带KRAS G12X突变的转移性PDAC患者中，接受每日一次300毫克剂量RMC-6236治疗患者的中位无进展生存期（PFS）为8.8个月，携带任何类型RAS突变的患者中，中位PFS为8.5个月。KRAS G12X突变患者的6个月生存率达100%，携带任何类型RAS突变患者的6个月生存率为97%。目前，RMC-6236正在两项3期临床试验中接受评估，用于治疗PDAC和非小细胞肺癌（NSCLC）患者。Icotrokinra：口服IL-23受体多肽抑制剂图片来源：PubChemIcotrokinra是Protagonist Therapeutics和强生（Johnson & Johnson）公司联合开发的IL-23受体口服多肽抑制剂。Icotrokinra能够以个位数的皮摩尔级亲和力与IL-23受体结合，并对人类T细胞中的IL-23信号转导产生强效的选择性抑制作用。近日公布的关键性3期临床试验结果显示，每日一次icotrokinra显著改善了中度至重度斑块型银屑病患者的皮肤状况，并具有良好的安全性。第16周时，65%的icotrokinra组患者达到研究者总体评估（IGA）评分为0/1（皮肤症状清除或几乎清除），50%的患者达到银屑病面积与严重程度指数（PASI）改善至少90%（PASI 90），而安慰剂组在这两个指标的数值分别仅为8%和4%。到第24周，患者缓解率进一步提高，74%的患者达到IGA评分为0/1，46%达到IGA 0分；65%的患者达到PASI 90，40%达到PASI 100。Laroprovstat（AZD0780）：口服PCSK9小分子抑制剂图片来源：猎药人官网AZD0780是阿斯利康（AstraZeneca）公司开发的潜在“first-in-class”口服PCSK9小分子抑制剂。PCSK9是降低低密度脂蛋白胆固醇（LDL-C）已经验证的靶点，不过目前的获批疗法均需要患者定期接受注射。口服PCSK9调节剂可能给患者提供更便捷的用药方式。去年5月，阿斯利康公布了AZD0780的首个人体临床试验结果。数据显示，在未经治疗的高胆固醇血症患者中，AZD0780在基于瑞舒伐他汀治疗的基础上，显示出52%（95% CI：57%，45%）的LDL-C水平显著下降，与基线相比患者的LDL-C总体下降幅度达78%。此外，比较进食与空腹服药的初步数据表明AZD0780对进食具有灵活性。未报告严重不良事件，AZD0780显示良好的耐受性。目前AZD0780处于2期临床开发阶段。HRO761：别构WRN抑制剂图片来源：猎药人官网HRO761是诺华（Novartis）公司开发的非共价别构WRN抑制剂。WRN是DNA解旋酶RecQ家族的成员之一。DNA解旋酶是一类在DNA或RNA复制过程中起到催化双链DNA或RNA解开的生物酶，参与了DNA复制、修复、转录、重组以及端粒的维持等细胞代谢过程，在维持染色体的稳定性中具有重要的作用。此前研究发现，WRN和微卫星不稳定性高（MSI-H）癌症之间具有合成致死的关系。HRO761通过与WRN在D1和D2解旋酶结构域的界面上发生别构结合，使WRN锁定在非活性构象中。HRO761抑制WRN的活性可选择性导致MSI-H癌细胞的DNA损伤以及抑制癌细胞的生长。此外，HRO761还能在MSI-H细胞中导致WRN的降解。目前，HRO761治疗实体瘤的1期临床试验正在进行中。VVD-214：共价别构WRN抑制剂图片来源：猎药人官网VVD-214是由拜耳（Bayer）公司旗下的Vividion Therapeutics和罗氏（Roche）联合开发的共价别构WRN抑制剂。WRN是MSI-H肿瘤的合成致死靶点。研究人员使用化学蛋白质组学（chemoproteomics）赋能的发现方法，筛选出这款WRN抑制剂。它在MSI-H结直肠癌细胞系和异种移植肿瘤模型中表现出强力抗癌活性。目前罗氏正在1期临床试验中评估它用于治疗MSI-H癌症的效果。Inavolisib：口服PI3Kα突变体选择性抑制剂和降解剂图片来源：猎药人官网Inavolisib是由罗氏旗下基因泰克（Genentech）开发的PI3Kα抑制剂，具有高度PI3Kα突变体选择性，并且能够特异性触发PI3Kα蛋白突变体的降解。通过这种独特的双重作用机制，inavolisib可能为激素受体（HR）阳性/人类表皮生长因子受体2（HER2）阴性、PIK3CA突变的晚期乳腺癌患者提供耐受良好、持久的疾病控制和潜在改善的结局。它在2024年10月获得FDA的批准（商品名Itovebi），与CDK4/6抑制剂Ibrance（palbociclib）和氟维司群（fulvestrant）联用，治疗肿瘤携带PIK3CA突变、内分泌治疗耐药、HR阳性、HER2阴性局部晚期或转移性乳腺癌成年患者，这些患者在接受辅助内分泌治疗时或完成辅助内分泌治疗后疾病复发。罗氏表示，它具有成为“best-in-class”PI3Kα抑制剂的潜力。KT-474（SAR444656）：口服IRAK4靶向蛋白降解剂图片来源：猎药人官网KT-474（SAR444656）是由Kymera Therapeutics和赛诺菲（Sanofi）联合开发的潜在“first-in-class”的IRAK4降解剂。IRAK4是myddosome蛋白复合体中的关键组分，通过白细胞介素-1（IL-1）和toll样受体（TLR）参与调控免疫反应的信号传导过程。IL-1和toll样受体在启动针对入侵病原体的免疫反应中扮演着关键角色。IRAK4是一种支架激酶，处于先天性免疫反应与适应性免疫反应的交汇点，通过其激酶活性和支架功能执行多重作用。KT-474利用靶向蛋白降解完全消除IRAK4，会影响其激酶和支架功能，因此有可能实现广泛、耐受性良好的抗炎作用，提供多种免疫炎症疾病的新治疗途径。此前公布的1期临床试验结果显示，在治疗特应性皮炎时，KT-474表现出可喜的活性。中重度患者在接受治疗28天后，瘙痒程度减轻63%，湿疹面积和严重度指数（EASI）评分下降36%。赛诺菲公司计划扩大正在进行的化脓性汗腺炎和特应性皮炎的2期临床试验，以更快地将这款创新疗法推进至关键性临床研究阶段。NX-5948：口服布鲁顿氏酪氨酸激酶（BTK）降解剂图片来源：猎药人官网NX-5948是Nurix公司开发的BTK靶向蛋白降解剂，它可以穿越血脑屏障，并且可降解野生型和突变型BTK蛋白。去年10月公布的早期临床试验结果显示，接受NX-5948治疗的9名复发/难治性华氏巨球蛋白血症（WM）患者中，7例患者（77.8%）出现客观缓解，两例患者病情稳定（22.2%）。所有7例缓解均在8周的首次评估中观察到，其中5例患者仍在接受治疗，2例患者治疗时间超过一年。不论患者基线MYD88和CXCR4的突变状态如何，均观察到应答。参考资料：[1] Top 12 Most Popular Drug Hunter Case Studies of 2024. Retrieved March 12, 2025, from https://drughunter.com/articles/top-12-most-popular-drug-hunter-case-studies-of-2024[2] AACR San Diego 2024: New Drugs on the Horizon + RMC-6236. Retrieved March 12, 2025, from https://drughunter.com/articles/aacr-san-diego-2024-new-drugs-on-the-horizon-rmc-6236[3] AZD0780, an oral PCSK9 inhibitor demonstrated significant LDL-C reduction on top of statin in Phase I trial. Retrieved March 12, 2025, from https://www.astrazeneca.com/media-centre/medical-releases/azd0780-an-oral-pcsk9-inhibitor-demonstrated-significant-ldl-c-reduction-on-top-of-statin-in-phase-i-trial.html[4] An Oral Small Molecule PCSK9 Inhibitor Disclosed by AstraZeneca. Retrieved March 12, 2025, from https://drughunter.com/molecule/azd0780[5] A Covalent Allosteric WRN Helicase Inhibitor Stemming from Chemoproteomics Screening. Retrieved March 12, 2025, from https://drughunter.com/molecule/vvd-214-ro7589831[6] Molecule One-Pager: KT-474 (SAR444656). Retrieved March 12, 2025, from https://drughunter.com/resource/molecule-one-pager-kt-474-sar444656[7] Icotrokinra results show potential to set a new standard of treatment in plaque psoriasis. Retrieved March 12, 2025, from https://www.jnj.com/media-center/press-releases/icotrokinra-results-show-potential-to-set-a-new-standard-of-treatment-in-plaque-psoriasis[8] The Highly Potent and CNS-Active NX-5948 Shows BTK Degradation in Patients. Retrieved March 12, 2025, from https://drughunter.com/molecule/nx-5948[9] Revolution Medicines Presents Initial Data from RMC-9805 Monotherapy Study in Patients with Advanced Pancreatic Ductal Adenocarcinoma. Retrieved March 12, 2025, from https://ir.revmed.com/news-releases/news-release-details/revolution-medicines-presents-initial-data-rmc-9805-monotherapy[10] Molecules of the Year Nominees. Retrieved March 18, 2025, from https://drughunter.com/molecules-of-the-month/2024/2024[11] Suzetrigine (VX-548): The 2024 Molecule of the Year. Retrieved April 9, 2025, from https://drughunter.com/articles/suzetrigine-vx-548-the-2024-molecule-of-the-year免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新

临床2期

100 项与 Laroprovstat 相关的药物交易

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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
动脉粥样硬化	临床3期	美国	AstraZeneca PLC	2025-05-30
动脉粥样硬化	临床3期	日本	AstraZeneca PLC	2025-05-30
动脉粥样硬化	临床3期	阿根廷	AstraZeneca PLC	2025-05-30
动脉粥样硬化	临床3期	澳大利亚	AstraZeneca PLC	2025-05-30
动脉粥样硬化	临床3期	巴西	AstraZeneca PLC	2025-05-30
动脉粥样硬化	临床3期	保加利亚	AstraZeneca PLC	2025-05-30
动脉粥样硬化	临床3期	加拿大	AstraZeneca PLC	2025-05-30
动脉粥样硬化	临床3期	智利	AstraZeneca PLC	2025-05-30
动脉粥样硬化	临床3期	捷克	AstraZeneca PLC	2025-05-30
动脉粥样硬化	临床3期	德国	AstraZeneca PLC	2025-05-30

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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


NCT06173570 (PURSUIT, Pubmed \| J Am Coll Cardiol) 人工标引	临床2期	高胆固醇血症	426	AZD0780	淵鏇蓋膚齋鏇鹽簾夢鑰(窪遞蓋鑰遞餘窪憲範鹹) = 鏇衊鑰蓋艱鑰襯簾糧齋艱衊餘衊簾鹹襯構襯鹹 (鬱簾願製淵範製網廠鑰 )	积极	2025-03-27
NCT06173570 (PURSUIT, Pubmed \| J Am Coll Cardiol) 人工标引	临床2期	高胆固醇血症	426	AZD0780 1mg	觸淵獵蓋齋淵衊遞夢艱(鬱艱簾鹹鬱夢繭顧齋鹹) = 膚選構膚鏇糧淵製網淵蓋憲簾鑰選淵窪鹹餘鹹 (艱製齋範餘選夢簾窪製 )	积极	2025-03-27
NCT05384262 (Company_Website) 人工标引	临床1期	高脂血症	-	AZD0780	繭餘遞淵膚製願鹽範顧(遞鏇顧鹹鹽網蓋網糧範) = None 艱鹽鏇鏇積蓋願襯糧夢 (觸鑰範糧積網糧糧膚鏇 )	积极	2024-05-29