更新于：2024-06-24
Zerlasiran
更新于：2024-06-24
概要
基本信息
非在研机构- |
最高研发阶段临床2期 |
首次获批日期- |
最高研发阶段(中国)- |
特殊审评- |
序列信息
Sequence Code 452929085
来源: *****
Sequence Code 452929086
来源: *****
关联
2
项与 Zerlasiran 相关的临床试验A Multi-centre, Randomised, Double-blind, Placebo-controlled, Phase 2 Study to Investigate Efficacy, Safety and Tolerability of SLN360 in Participants With Elevated Lipoprotein(a) at High Risk of Atherosclerotic Cardiovascular Disease Events
A Randomised, Double-blind, Placebo Controlled, First-in-human Study to Investigate the Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Response of SLN360 in Subjects With Elevated Lipoprotein(a)
100 项与 Zerlasiran 相关的临床结果
登录后查看更多信息
100 项与 Zerlasiran 相关的转化医学
登录后查看更多信息
100 项与 Zerlasiran 相关的专利（医药）
登录后查看更多信息
14
项与 Zerlasiran 相关的文献（医药）2023-11-01Clinical therapeutics
The Promise of PCSK9 and Lipoprotein(a) as Targets for Gene Silencing Therapies
Review
作者: Watts, Gerald F ; Chan, Dick C
PURPOSE:
High plasma concentrations of LDL and lipoprotein(a) (Lp[a]) are independent and causal risk factors for atherosclerotic cardiovascular disease (ASCVD). There is an unmet therapeutic need for high-risk patients with elevated levels of LDL-C and/or Lp(a). Recent advances in the development of nucleic acids for gene silencing (ie, triantennary N-acetylgalactosamine conjugated antisense-oligonucleotides [ASOs] and small interfering RNA [siRNA]) targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) and Lp(a) offer effective and sustainable therapies.
METHODS:
Related articles in the English language were identified through a search for original and review articles in the PubMed database using the following key terms: cardiovascular disease, dyslipidemia, PCSK9 inhibitors, Lp(a), LDL-cholesterol, familial hypercholesterolemia, siRNA, and antisense oligonucleotide and clinical trials (either alone or in combination).
FINDINGS:
Inclisiran, the most advanced siRNA-treatment targeting hepatic PCSK9, is well tolerated, producing a >30% reduction on LDL-C levels in randomized controlled trials. Pelacarsen is the most clinical advanced ASO, whereas olpasiran and SLN360 are the 2 siRNAs directed against the mRNA of the LPA gene. Evidence suggests that all Lp(a)-targeting agents are safe and well tolerated, with robust and sustained reduction in plasma Lp(a) concentration up to 70% to 90% in individuals with elevated Lp(a) levels.
IMPLICATIONS:
Cumulative evidence from clinical trials supports the value of ASO and siRNA therapies targeting the synthesis of PCSK9 and Lp(a) for lowering LDL-C and Lp(a) in patients with established ASCVD or high risk of ASCVD. Further research is needed to examine whether gene silencing therapy could improve clinical outcomes in patients with elevated LDL and/or Lp(a) levels. Confirmation of the tolerability and cost-effectiveness of long-term inhibition of PCSK9 and Lp(a) with this approach is essential.
2023-10-01Pharmacotherapy
Role of lipoprotein(a) in atherosclerotic cardiovascular disease: A review of current and emerging therapies.
Review
作者: Dixon, Dave L ; Mehta, Anurag ; Bucheit, John D ; Alhomoud, Ibrahim S ; Kelly, Michael S ; Talasaz, Azita ; Sisson, Evan M ; Brown, Roy
Lipoprotein(a), or Lp(a), is structurally like low-density lipoprotein (LDL) but differs in that it contains glycoprotein apolipoprotein(a) [apo(a)]. Due to its prothrombotic and proinflammatory properties, Lp(a) is an independent risk factor for atherosclerotic cardiovascular disease (ASCVD) and aortic valve stenosis. Lp(a) levels are genetically determined, and it is estimated that 20%-25% of the global population has an Lp(a) level ≥50 mg/dL (or ≥125 nmol/L). Diet and lifestyle interventions have little to no effect on Lp(a) levels. Lipoprotein apheresis is the only approved treatment for elevated Lp(a) but is time-intensive for the patient and only modestly effective. Pharmacological approaches to reduce Lp(a) levels and its associated risks are of significant interest; however, currently available lipid-lowering therapies have limited effectiveness in reducing Lp(a) levels. Although statins are first-line agents to reduce LDL cholesterol levels, they modestly increase Lp(a) levels and have not been shown to change Lp(a)-mediated ASCVD risk. Alirocumab, evolocumab, and inclisiran reduce Lp(a) levels by 20-25%, yet the clinical implications of this reduction for Lp(a)-mediated ASCVD risk are uncertain. Niacin also lowers Lp(a) levels; however, its effectiveness in mitigating Lp(a)-mediated ASCVD risk remains unclear, and its side effects have limited its utilization. Recommendations for when to screen and how to manage individuals with elevated Lp(a) vary widely between national and international guidelines and scientific statements. Three investigational compounds targeting Lp(a), including small interfering RNA (siRNA) agents (olpasiran, SLN360) and an antisense oligonucleotide (pelacarsen), are in various stages of development. These compounds block the translation of messenger RNA (mRNA) into apo(a), a key structural component of Lp(a), thereby substantially reducing Lp(a) synthesis in the liver. The purpose of this review is to describe current recommendations for screening and managing elevated Lp(a), describe the effects of currently available lipid-lowering therapies on Lp(a) levels, and provide insight into emerging therapies targeting Lp(a).
2023-10-01Current atherosclerosis reports
Treatment of Lp(a): Is It the Future or Are We Ready Today?
Review
作者: Tselepis, Alexandros D
PURPOSE OF REVIEW:
The goal of this review is to present the pharmacodynamic effectiveness as well as the clinical efficacy and safety of investigational antisense oligonucleotides (ASOs) and small interference RNAs (siRNAs) drugs that specifically target lipoprotein(a) (Lp(a)). The review will discuss whether the existing lipid-lowering therapies are adequate to treat high Lp(a) levels or whether it is necessary to use the emerging new therapeutic approaches which are based on the current RNA technologies.
RECENT FINDINGS:
Lipoprotein(a) (Lp(a)) is a causal risk factor for atherosclerotic cardiovascular disease (ASCVD), independent of other conventional risk factors. High Lp(a) levels are also independently associated with an increased risk of aortic stenosis progression rate. Plasma Lp(a) levels are primarily genetically determined by variation in the LPA gene coding for apo(a). All secondary prevention trials have demonstrated that the existing hypolipidemic therapies are not adequate to reduce Lp(a) levels to such an extent that could lead to a substantial reduction of ASCVD risk. This has led to the development of new drugs that target the mRNA transcript of LPA and efficiently inhibit Lp(a) synthesis leading to potent Lp(a) reduction. These new drugs are the ASO pelacarsen and the siRNAs olpasiran and SLN360. Recent pharmacodynamic studies showed that all these drugs potently reduce Lp(a) up to 98%, in a dose-dependent manner. Ongoing clinical trials will determine the Lp(a)-lowering efficacy, tolerability, and safety of these drugs as well as their potential effectiveness in reducing the ASCVD risk attributed to high plasma Lp(a) levels. We are not ready today to significantly reduce plasma Lp(a). Emerging therapies potently decrease Lp(a) and ongoing clinical trials will determine their effectiveness in reducing ASCVD risk in subjects with high Lp(a) levels.
76
项与 Zerlasiran 相关的新闻（医药）2024-06-22
·医药地理
2024-06-22
·药融圈
siRNA临床结果临床2期
2024-06-20
·医药魔方
siRNA临床3期临床结果临床2期
100 项与 Zerlasiran 相关的药物交易
登录后查看更多信息
研发状态
10 条进展最快的记录, 后查看更多信息
登录
| 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2期 | 澳大利亚 | 2023-01-03 | |
| 动脉粥样硬化 | 临床2期 | 捷克 | 2023-01-03 | |
| 动脉粥样硬化 | 临床2期 | 丹麦 | 2023-01-03 | |
| 动脉粥样硬化 | 临床2期 | 荷兰 | 2023-01-03 | |
| 动脉粥样硬化 | 临床2期 | 斯洛伐克 | 2023-01-03 | |
| 动脉粥样硬化 | 临床2期 | 南非 | 2023-01-03 | |
| 动脉粥样硬化 | 临床2期 | 英国 | 2023-01-03 | |
| 心血管疾病 | 临床2期 | - | - | |
| 高脂蛋白血症 | 临床1期 | 美国 | 2020-11-18 | |
| 高脂蛋白血症 | 临床1期 | 澳大利亚 | 2020-11-18 |
登录后查看更多信息
临床结果
临床结果
适应症
分期
评价
查看全部结果
N/A | - | Zerlasiran 300 mg (a single subcutaneous dose) | 願餘衊鬱構艱獵蓋壓觸(獵襯製壓齋醖製獵製範) = There were no serious adverse events. 繭獵夢築選壓簾餘蓋鑰 (鏇繭鏇齋廠餘憲鑰繭壓 ) | 积极 | 2024-04-08 | ||
Zerlasiran 600 mg (a single subcutaneous dose) | |||||||
临床2期 | 178 | 鬱築簾構襯鑰齋夢鹹膚(廠膚蓋憲鑰鹹製衊積憲) = 壓遞齋鬱餘積鏇繭壓遞 鬱繭憲鬱積築積醖衊鑰 (鬱壓齋淵願膚選製艱鏇 ) | 积极 | 2024-03-13 | |||
Placebo | - | ||||||
临床1期 | 36 | 鏇艱鬱簾簾蓋遞窪選簾(顧構糧範願餘糧製顧糧) = 糧襯築餘壓繭積衊範衊 鹽積範願遞積遞構構遞 (範選鬱廠糧鹽簾簾夢網 ) 更多 | 积极 | 2023-11-01 | |||
Placebo | - | ||||||
临床1期 | - | 32 | Placebo | 製壓獵壓齋廠蓋憲艱選(積顧淵繭蓋獵壓觸窪選) = One participant experienced 2 serious adverse event episodes: admission to the hospital for headache following SARS-CoV-2 vaccination and later for complications of cholecystitis, both of which were judged to be unrelated to study drug. 願鏇鏇襯鏇繭壓選襯夢 (壓鹹遞衊願網艱願構範 ) | 积极 | 2022-04-03 | |
N/A | IL-1β | Tumor Necrosis Factor-α | - | 憲選淵遞壓構廠艱製艱(糧蓋鹽壓糧鬱鹽繭構鹹) = 簾獵艱蓋襯壓築廠餘積 繭構齋夢簾選鹹鏇鏇壓 (艱構夢膚襯範簾淵願構 ) 更多 | 积极 | 2011-05-01 |
登录后查看更多信息
转化医学
使用我们的转化医学数据加速您的研究。
登录
或
药物交易
使用我们的药物交易数据加速您的研究。
登录
或
核心专利
使用我们的核心专利数据促进您的研究。
登录
或
临床分析
紧跟全球注册中心的最新临床试验。
登录
或
批准
利用最新的监管批准信息加速您的研究。
登录
或
特殊审评
只需点击几下即可了解关键药物信息。
登录
或
立即开始免费试用!
智慧芽新药情报库是智慧芽专为生命科学人士构建的基于AI的创新药情报平台，助您全方位提升您的研发与决策效率。
立即开始数据试用!
智慧芽新药库数据也通过智慧芽数据服务平台，以API或者数据包形式对外开放，助您更加充分利用智慧芽新药情报信息。
生物序列数据库
生物药研发创新
免费使用
化学结构数据库
小分子化药研发创新
免费使用