更新于：2024-06-29
Olpasiran
更新于：2024-06-29
概要
基本信息
药物类型 siRNA |
别名 ARC LPA、ARC-LPA、ARO LPA + [3] |
作用机制 脂蛋白（a）抑制剂 |
非在研适应症- |
在研机构 |
非在研机构- |
最高研发阶段临床3期 |
首次获批日期- |
最高研发阶段(中国)临床3期 |
特殊审评突破性疗法 (中国) |
序列信息
Sequence Code 31610133
来源: *****
Sequence Code 31611198
来源: *****
关联
9
项与 Olpasiran 相关的临床试验A Randomized, Placebo- and Positive-controlled, Crossover Study to Assess the Effect of Olpasiran (AMG 890) on QT/QTc Intervals in Healthy Subjects
一项在动脉粥样硬化性心血管疾病伴脂蛋白（a）升高患者中评估Olpasiran对主要心血管事件的影响的双盲、随机、安慰剂对照、多中心研究
A Double-blind, Randomized, Placebo-controlled, Multicenter Study Assessing the Impact of Olpasiran on Major Cardiovascular Events in Participants With Atherosclerotic Cardiovascular Disease and Elevated Lipoprotein(a)
100 项与 Olpasiran 相关的临床结果
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100 项与 Olpasiran 相关的转化医学
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100 项与 Olpasiran 相关的专利（医药）
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65
项与 Olpasiran 相关的文献（医药）2024-01-23Annual review of pharmacology and toxicology
LP(a): Structure, Genetics, Associated Cardiovascular Risk, and Emerging Therapeutics
Review
作者: Almaadawy, Omar ; Tasdighi, Erfan ; Adhikari, Rishav ; Blaha, Michael J ; Leucker, Thorsten M
Lipoprotein(a) [Lp(a)] is a molecule bound to apolipoprotein(a) with some similarity to low-density lipoprotein cholesterol (LDL-C), which has been found to be a risk factor for cardiovascular disease (CVD). Lp(a) appears to induce inflammation, atherogenesis, and thrombosis. Approximately 20% of the world's population has increased Lp(a) levels, determined predominantly by genetics. Current clinical practices for the management of dyslipidemia are ineffective in lowering Lp(a) levels. Evolving RNA-based therapeutics, such as the antisense oligonucleotide pelacarsen and small interfering RNA olpasiran, have shown promising results in reducing Lp(a) levels. Phase III pivotal cardiovascular outcome trials [Lp(a)HORIZON and OCEAN(a)] are ongoing to evaluate their efficacy in secondary prevention of major cardiovascular events in patients with elevated Lp(a). The future of cardiovascular residual risk reduction may transition to a personalized approach where further lowering of either LDL-C, triglycerides, or Lp(a) is selected after high-intensity statin therapy based on the individual risk profile and preferences of each patient.
2023-12-01Heliyon
Aromadendrin inhibits PMA-induced cytokine formation/NF-κB activation in A549 cells and ovalbumin-induced bronchial inflammation in mice
Article
作者: Kim, Seung-Ho ; Seo, Da-Yun ; Lee, Jae-Won ; Ahn, Kyung-Seop ; Park, Jin-Mi ; Han, Sang-Bae ; Park, Ji-Won ; Lee, Juhyun
Hyperproduction of immune cell-derived inflammatory molecules and recruitment of immune cells promote the development of allergic asthma (AA). Aromadendrin (ARO) has various biological properties including anti-inflammatory effects. In this study, we evaluated the ameliorative effects of ARO on the development of AA in vitro and in vivo. Phorbol 12-myristate 13-acetate (PMA, 100 nM) was used to induce inflammation in A549 airway epithelial cells. The cohesion of A549 and eosinophil EOL-1 cells was studied. Ovalbumin (30 or 60 μg)/Alum (3 mg) mixture was adapted for AA induction in mice. ARO (5 or 10 mg/kg, p. o.) was administered to mice to investigate its ameliorative effect on AA development. Enzyme-linked immunosorbent assay, western blotting, and hematoxylin and eosin/periodic acid Schiff staining were performed to study the ameliorative effect of ARO on bronchial inflammation. In PMA-stimulated A549 cells, the upregulation of cytokines (interleukin [IL]-1β/IL-6/tumor necrosis factor alpha [TNF-α]/monocyte chemoattractant protein [MCP]-1]) and nuclear factor kappa B (NF-κB) activation was effectively reduced by ARO pretreatment. ARO suppressed the adhesion of A549 cells and eosinophils. In ovalbumin-induced AA mice, the levels of cells, such as eosinophils, Th2 cytokines, MCP-1 in bronchoalveolar lavage fluid, IgE in serum, and inducible nitric oxide synthase/cyclooxygenase-2 expression in the lung tissue were upregulated, which were all suppressed by ARO. In addition, the increase in cell inflow and mucus formation in the lungs of AA mice was reversed by ARO as per histological analysis. ARO also modulated NF-κB activation in the lungs of AA mice. Overall, the anti-inflammatory properties of ARO in vitro/in vivo studies of AA were notable. Thus, ARO has a modulatory effect on bronchial inflammation and may be a potential adjuvant for AA treatment.
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.
100 项与 Olpasiran 相关的药物交易
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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 |
|---|---|---|---|---|
| 动脉粥样硬化 | 临床3期 | 阿根廷 | 2022-11-30 | |
| 肝病 | 临床1期 | 美国 | 2022-09-13 |
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临床结果
临床结果
适应症
分期
评价
查看全部结果
临床2期 | 281 | 夢觸選夢範壓獵積鹹鏇(範積齋壓選夢製艱淵淵) = The results from the off-treatment extension period show that patients previously dosed with ≥75 mg of olpasiran sustained a ~40-50% placebo-adjusted percent reduction in Lp(a) nearly a year after the last dose. 餘廠壓積繭膚鑰製鹹製 (遞鏇鹽構夢積蓋襯廠鹽 ) | 积极 | 2023-08-26 | |||
placebo | |||||||
临床2期 | 281 | 積顧夢築鏇衊鏇鬱遞衊(選餘壓壓醖顧蓋鏇鬱淵) = 遞鏇構獵糧鹽積廠膚鏇 蓋鏇範鑰醖鏇廠襯膚淵 (鹹遞艱鏇襯鑰衊構醖襯 ) | - | 2022-11-06 | |||
積顧夢築鏇衊鏇鬱遞衊(選餘壓壓醖顧蓋鏇鬱淵) = 遞餘鏇廠獵醖顧膚繭膚 蓋鏇範鑰醖鏇廠襯膚淵 (鹹遞艱鏇襯鑰衊構醖襯 ) | |||||||
临床1期 | 27 | (Japanese participants) | 淵構選顧積廠壓願壓觸(壓鬱艱蓋築艱繭蓋積窪) = 餘願鑰願獵築積鏇蓋築 糧積鏇鹽衊構鏇廠衊製 (鬱憲鏇膚築簾繭簾獵鏇, 121.0) 更多 | 积极 | 2022-08-10 | ||
(Non-Japanese participants) | 淵構選顧積廠壓願壓觸(壓鬱艱蓋築艱繭蓋積窪) = 顧壓遞簾構餘簾簾選觸 糧積鏇鹽衊構鏇廠衊製 (鬱憲鏇膚築簾繭簾獵鏇, 71.3) 更多 | ||||||
临床2期 | 281 | 網糧觸製糧鹽簾衊遞積(膚醖蓋繭選憲憲顧襯衊) = These data demonstrated a significant reduction from baseline in Lp(a) of up to or greater than 90 percent 築構獵遞衊齋蓋衊艱鏇 (糧築蓋選願艱窪鑰衊顧 ) 更多 | 积极 | 2022-05-31 | |||
Placebo | |||||||
临床1期 | - | 64 | 壓鹽選簾餘糧蓋蓋襯衊(鏇繭夢襯願築鹹淵網襯) = The most common TEAEs were headache (10% AMG 890; 25% placebo) and upper respiratory tract infection (15% AMG 890; 13% placebo) 壓憲醖獵製憲網鏇齋範 (範鑰齋簾窪鏇繭構蓋窪 ) 更多 | 积极 | 2020-11-12 | ||
Placebo |
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