J3L-MC-EZEF:A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Investigate the Effect of Lepodisiran on the Reduction of Major Adverse Cardiovascular Events in Adults with Elevated Lipoprotein(a) who have Established Atherosclerotic Cardiovascular Disease or Are at Risk for a First Cardiovascular Event – ACCLAIM-Lp(a) - J3L-MC-EZEF

开始日期2024-09-04

申办/合作机构

Eli Lilly & Co.

CTR20242182 / Recruiting临床3期

一项在伴有脂蛋白(a)水平升高的确诊动脉粥样硬化性心血管疾病或发生首次心血管事件风险升高成人中评lepodisiran对主要不良心血管事件影响的3期、随机、双盲、平行、安慰剂对照研究-ACCLAIM-Lp(a)

在脂蛋白(a)水平升高的成人中评价lepodisiran 对主要不良心血管事件影响

开始日期2024-07-02

申办/合作机构

礼来苏州制药有限公司

[+2]

NCT06292013 / Recruiting临床3期

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Investigate the Effect of Lepodisiran on the Reduction of Major Adverse Cardiovascular Events in Adults With Elevated Lipoprotein(a) Who Have Established Atherosclerotic Cardiovascular Disease or Are at Risk for a First Cardiovascular Event - ACCLAIM-Lp(a)

The purpose of this study is to evaluate the efficacy of lepodisiran in reducing cardiovascular risk in participants with high lipoprotein(a) who have cardiovascular disease or are at risk of a heart attack or stroke. The study drug will be administered subcutaneously (SC) (under the skin).

开始日期2024-03-05

申办/合作机构

Eli Lilly & Co.

100 项与 Lepodisiran sodium 相关的临床结果

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100 项与 Lepodisiran sodium 相关的转化医学

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100 项与 Lepodisiran sodium 相关的专利（医药）

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项与 Lepodisiran sodium 相关的文献（医药）

2024-09-01·International Journal of Cardiology Cardiovascular Risk and Prevention

Lipoprotein (a) and lipid-lowering treatment from the perspective of a cardiac surgeon. An impact on the prognosis in patients with aortic valve replacement and after heart transplantation

Article

作者: Okopień, Bogusław ; Banach, Maciej ; Surma, Stanisław ; Zembala, Michał O

Lipoprotein(a) is a recognized risk factor for ASCVD. There is still no targeted therapy for Lp(a), however, drugs such as pelacarsen, olpasiran, zerlasiran, lepodisiran and muvalaplin are in clinical trials and have been shown to be effective in significantly reducing Lp(a) levels. Moreover, elevated Lp(a) levels significantly affect the prognosis of patients after aortic valve replacement (AVR) and heart transplantation (HTx). Therefore, the assessment of Lp(a) concentration in these patients will allow for a more accurate stratification of their cardiovascular risk, and the possibility of lowering Lp(a) will allow for the optimization of this risk. In this article, we summarized the most important information regarding the role of Lp(a) and lipid-lowering treatment in patients after AVR and HTx.

2024-09-01·European Journal of Clinical Investigation

New insights into the therapeutic options to lower lipoprotein(a)

Review

作者: Da Dalt, L ; Norata, G D ; Baragetti, A

AbstractBackgroundElevated levels of lipoprotein(a) [Lp(a)] represent a risk factor for cardiovascular disease including aortic valve stenosis, myocardial infarction and stroke. While the patho‐physiological mechanisms linking Lp(a) with atherosclerosis are not fully understood, from genetic studies that lower Lp(a) levels protect from CVD independently of other risk factors including lipids and lipoproteins. Hereby, Lp(a) has been considered an appealing pharmacological target.ResultsHowever, approved lipid lowering therapies such as statins, ezetimibe or PCSK9 inhibitors have a neutral to modest effect on Lp(a) levels, thus prompting the development of new strategies selectively targeting Lp(a). These include antisense oligonucleotides and small interfering RNAs (siRNAs) directed towards apolipoprotein(a) [Apo(a)], which are in advanced phase of clinical development. More recently, additional approaches including inhibitors of Apo(a) and gene editing approaches via CRISPR‐Cas9 technology entered early clinical development.ConclusionIf the results from the cardiovascular outcome trials, designed to demonstrate whether the reduction of Lp(a) of more than 80% as observed with pelacarsen, olpasiran or lepodisiran translates into the decrease of cardiovascular mortality and major adverse cardiovascular events, will be positive, lowering Lp(a) will become a new additional target in the management of patients with elevated cardiovascular risk.

2024-08-01·Current Problems in Cardiology

Elevated lipoprotein(a) levels: A crucial determinant of cardiovascular disease risk and target for emerging therapies

Review

作者: Alruwaili, Waleed ; Chaudhary, Mueed ; Chigurupati, Himaja Dutt ; Afzal, Zeeshan ; Cao, Huili ; Gonuguntla, Karthik ; Siddique, Muzammil ; Neppala, Sivaram ; Zafrullah, Fnu ; Sattar, Yasar ; Sandesara, Darshan ; Awad, Maan ; Farman, Ali

Cardiovascular disease (CVD) remains a significant global health challenge despite advancements in prevention and treatment. Elevated Lipoprotein(a) [Lp(a)] levels have emerged as a crucial risk factor for CVD and aortic stenosis, affecting approximately 20 of the global population. Research over the last decade has established Lp(a) as an independent genetic contributor to CVD and aortic stenosis, beginning with Kare Berg's discovery in 1963. This has led to extensive exploration of its molecular structure and pathogenic roles. Despite the unknown physiological function of Lp(a), studies have shed light on its metabolism, genetics, and involvement in atherosclerosis, inflammation, and thrombosis. Epidemiological evidence highlights the link between high Lp(a) levels and increased cardiovascular morbidity and mortality. Newly emerging therapies, including pelacarsen, zerlasiran, olpasiran, muvalaplin, and lepodisiran, show promise in significantly lowering Lp(a) levels, potentially transforming the management of cardiovascular disease. However, further research is essential to assess these novel therapies' long-term efficacy and safety, heralding a new era in cardiovascular disease prevention and treatment and providing hope for at-risk patients.

项与 Lepodisiran sodium 相关的新闻（医药）

2024-11-19

·Firstwordpharma

AHA24: Lilly’s muvalaplin achieves robust Lp(a) reduction in mid-stage study

Eli Lilly said its investigational once-daily oral selective lipoprotein(a) [Lp(a)] inhibitor, muvalaplin, met the primary endpoint of a mid-stage trial, demonstrating significant Lp(a) reductions over a 12-week period. The data were presented at the American Heart Association’s (AHA) scientific sessions on Monday and concurrently published in JAMA.According to the company, muvalaplin, a small molecule inhibitor, works by blocking the interaction between apolipoprotein(a) [apo(a)] and apolipoprotein B, which is critical for Lp(a) formation. “While injectable approaches for Lp(a) are currently in Phase III development…these are the first positive Phase II data for an oral approach,” said Ruth Gimeno, group VP of diabetes and metabolic research at Lilly Research Labs. The Phase II KRAKEN study enrolled 233 participants with Lp(a) levels of ≥175 nmol/L and atherosclerotic cardiovascular disease, diabetes, or familial hypercholesterolaemia. Participants were randomised to receive oral muvalaplin at 10 mg, 60 mg or 240 mg doses, or placebo for 12 weeks. The primary endpoint was percentage change in the Lp(a) concentration at week 12. Results showed that muvalaplin at all three doses significantly lowered Lp(a) levels at 12 weeks, with placebo-adjusted reductions of up to 85.8% using the intact Lp(a) assay and up to 70.0% with the apo(a) assay at the highest dose. Furthermore, 64.2%, 95.9% and 96.7% of participants in the 10 mg, 60 mg and 240 mg muvalaplin groups, respectively, achieved Lp(a) levels below 125 nmol/L using the intact Lp(a) assay, compared with 6.0% in the placebo group at week 12. Using the apo(a) assay, 38.9%, 81.9% and 77.4% of participants in the same groups reached the same Lp(a) threshold, compared with 3.6% in the placebo group. Meanwhile, muvalaplin recipients in the 60 mg and 240 mg groups also achieved significant reductions in apoB. With regard to safety, adverse event rates were comparable in the muvalaplin and placebo groups. No deaths were reported, and discontinuations due to adverse effects were low. Besides muvalaplin, Lilly’s cardiovascular (CV) disease pipeline includes the Lp(a)-targeting siRNA lepodisiran licensed in 2018 from Dicerna Pharmaceuticals, which was later acquired by Novo Nordisk. Lilly is also exploring its GLP-1 agonist Mounjaro/Zepbound (tirzepatide) to improve CV outcomes in patients with diabetes and/or obesity.

并购临床结果AHA会议临床2期

2024-11-19

·医药魔方

高达85%！礼来潜在首创口服小分子显著降低心血管事件高风险成人Lp(a)水平

11月18日，礼来宣布每日口服一次脂蛋白（a）[Lp(a)]选择性抑制剂muvalaplin 的一项II期研究结果。研究表明，muvalaplin能显著降低成人体内升高的Lp（a）水平，达到了主要终点（即从基线到第12周的Lp（a）变化百分比）。礼来正在评估一种强效、多价的小分子药物muvalaplin，它通过阻断载脂蛋白（a）[apo（a）]和载脂蛋白B（apoB）之间的初始相互作用来抑制Lp（a）的形成。在美国，约有 20% 的人，即大约 6300 万人，Lp（a）水平较高。Lp（a）水平升高可使心脏病发作的风险增加一倍甚至两倍，并与其他心血管问题相关。在为期12周的研究中，与安慰剂相比，muvalaplin（10mg、60mg和240mg）能明显降低Lp（a）水平。使用完整Lp（a）测定法，安慰剂调整后的降低率高达85.8%，使用apo（a）测定法，降低率高达70.0%。具体来说，使用完整Lp（a）测定法，降幅分别为47.6%（10mg）、81.7%（60mg）和85.8%（240mg）；使用apo（a）测定法，降幅分别为40.4%（10mg）、70.0%（60mg）和68.9%（240mg）。 Muvalaplin的所有三个测试剂量（10mg、60mg和240mg）都达到了次要终点。三种测试剂量在降低Lp（a）阈值方面均达到了统计学意义，60mg和 240mg剂量在降低apoB方面也达到了统计学意义。这些数据还表明使用完整Lp（a）检测法，在第 12 周达到Lp（a）水平低于 125 nmol/L 的参与者比例分别为64.2%（10mg）、95.9%（60mg）和 96.7%（240mg），而安慰剂组为 6.0%。通过apo（a）检测，Lp（a）水平低于125 nmol/L的参与者比例为38.9%（10mg）、81.9%（60mg）和77.4%（240mg），而安慰剂组为3.6%。所有剂量的apoB水平都有所下降，安慰剂调整后的降幅分别为8.9%（10mg）、13.1%（60mg）和16.1%（240mg）。 muvalaplin组和安慰剂组的不良反应相似。安慰剂组中有 14.9%、10 毫克组中有 5.9%、60 毫克组中有 14.3%、240 毫克组中有 14.7%发生了与研究药物相关的治疗突发不良事件。各治疗组导致停药的不良事件发生率从0到8.8%不等，均为单一事件，分布于各系统器官。研究中没有死亡报告。 “高水平的Lp（a）已被证明是动脉粥样硬化性心血管疾病的一个重要风险因素，影响着全球十多亿成年人，"维多利亚心脏医院和研究所所长、澳大利亚莫纳什大学心脏病学教授Stephen J. Nicholls表示：“目前的降胆固醇疗法未被批准用于降低Lp（a）水平，这凸显了心血管疾病患者的需求尚未得到满足。这些数据代表了所需的科学进步，有可能通过每日一次的药片降低心脏病发作或中风等心血管事件的风险。” “虽然治疗Lp（a）的注射方法目前正处于III期开发阶段，包括礼来自己的lepodisiran项目，但这些是口服方法的首个积极的II期数据，"礼来研究实验室糖尿病和代谢研究集团副总裁 Ruth Gimeno表示：“我们很高兴看到这些有前景的结果，并期待着进一步探索muvalaplin的下一步发展。” 此前，礼来的一年一针RNAi疗法Lepodisiran（LY3819469）也有惊艳表现，其首个人体研究结果显示单剂量Lepodisiran可将有害风险因子Lp(a)降低94%，并持续近一年。 Copyright © 2024 PHARMCUBE. All Rights Reserved. 欢迎转发分享及合理引用，引用时请在显要位置标明文章来源；如需转载，请给微信公众号后台留言或发送消息，并注明公众号名称及ID。免责申明：本微信文章中的信息仅供一般参考之用，不可直接作为决策内容，医药魔方不对任何主体因使用本文内容而导致的任何损失承担责任。

临床结果临床2期临床成功

2024-11-19

·Outsourcing Pharma

Eli Lilly announces positive Phase 2 results for Muvalaplin against heart disease

Yesterday, Eli Lilly and Company revealed promising Phase 2 results for its investigational small molecule drug, Muvalaplin, against cardiovascular events. The drug met its primary and secondary endpoints at 12 weeks, revealing a reduction of lipoprotein(a)– Lp(a)– levels by up to 85% in adults with high risk for cardiovascular events. Muvalaplin selectively inhibits Lp(a), a genetic risk factor for heart disease. In the U.S., about 63 million people are known to have high levels of Lp(a). Lp(a) can form plaques in the walls of blood vessels, disrupting blood flow to essential organs, including the heart, kidneys, lungs, and brain. An excessive accumulation of Lp(a) plaques can result in heart attack, stroke, or other cardiovascular diseases. Eli Lilly’s Muvalaplin blocks the interaction between apolipoprotein(a) and apolipoprotein B, preventing the formation of Lp(a), and thereby lowering the risk of cardiovascular diseases. "High levels of Lp(a) have been shown to be a significant risk factor for atherosclerotic cardiovascular disease, affecting over one billion adults globally," explained Stephen J. Nicholls, Director of the Victorian Heart Hospital and Institute, and Professor of Cardiology at Monash University, Australia, in a press release. "Current cholesterol-lowering therapies are not approved to lower Lp(a) levels, highlighting an unmet need for people living with cardiovascular disease. These data represent a needed scientific advancement with the potential to reduce the risk of cardiovascular events such as heart attacks or strokes with a once-daily pill." googletag.cmd.push(function () { googletag.display('text-ad1'); }); In the Phase 2 study, Muvalaplin was given to participants in three different dosages– 10mg, 60mg, and 240mg– and tested against a placebo. At all dosages, Muvalaplin showed a reduction of Lp(a) levels compared to the placebo. The researchers measured the reductions using an Lp(a) assay– up to 85.8% Lp(a) reduction– and an apolipoprotein(a) assay– up to 70% Lp(a) reduction– at the highest dosage. "While injectable approaches for Lp(a) are currently in Phase 3 development, including Lilly's own lepodisiran program, these are the first positive Phase 2 data for an oral approach," said Ruth Gimeno, Group Vice President of Diabetes and Metabolic Research at Lilly Research Laboratories, in a press release. "We are very pleased to see these promising results and look forward to further exploring next steps for Muvalaplin." Cardiovascular disease treatments have seen a major surge in interest from big pharma companies. Just recently, AstraZeneca entered into a licensing deal worth up to $2 billion with the Chinese company CSPC Pharmaceutical Group to further develop its oral small molecule drug targeting Lp(a)– a rival to Lilly’s Muvalaplin.

临床结果临床2期临床3期引进/卖出AHA会议

100 项与 Lepodisiran sodium 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	澳大利亚	Eli Lilly & Co.	2024-03-05
动脉粥样硬化	临床3期	印度	Eli Lilly & Co.	2024-03-05
动脉粥样硬化	临床3期	日本	Eli Lilly & Co.	2024-03-05
动脉粥样硬化	临床3期	德国	Eli Lilly & Co.	2024-03-05
动脉粥样硬化	临床3期	中国	Eli Lilly & Co.	2024-03-05
动脉粥样硬化	临床3期	奥地利	Eli Lilly & Co.	2024-03-05
动脉粥样硬化	临床3期	中国台湾	Eli Lilly & Co.	2024-03-05
动脉粥样硬化	临床3期	法国	Eli Lilly & Co.	2024-03-05
动脉粥样硬化	临床3期	美国	Eli Lilly & Co.	2024-03-05
动脉粥样硬化	临床3期	丹麦	Eli Lilly & Co.	2024-03-05