弗洛西单抗(Frovocimab) - 药物靶点：PCSK9_专利_临床

概要

基本信息

药物类型

单克隆抗体

别名

Frovocimab (USAN)

靶点

PCSK9

作用机制

PCSK9抑制剂(前蛋白转化酶枯草杆菌蛋白酶Kexin-9抑制剂)

治疗领域

内分泌与代谢疾病

在研适应症-

非在研适应症

高低密度脂蛋白胆固醇血症原发性高胆固醇血症

原研机构

Eli Lilly & Co.

在研机构-

非在研机构

Eli Lilly & Co.

最高研发阶段无进展临床2期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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序列信息

Sequence Code 32694L

来源: *****

Sequence Code 32689H

来源: *****

关联

7

项与弗洛西单抗相关的临床试验

EUCTR2013-000622-55-NL / Not yet recruitingN/A

A Phase 2 Efficacy and Safety Dose-Ranging Study of LY3015014 in Patients with Primary Hypercholesterolemia

开始日期2013-08-13

申办/合作机构

Eli Lilly & Co.

JPRN-jRCT2080222170 / Unknown status临床2期

A Phase 2 Efficacy and Safety Dose-Ranging Study of LY3015014 in Patients with Primary Hypercholesterolemia

开始日期2013-08-05

申办/合作机构

Eli Lilly Japan KK

NCT01890967 / Completed临床2期

A Phase 2 Efficacy and Safety Dose-Ranging Study of LY3015014 in Patients With Primary Hypercholesterolemia

This study is designed to define the amount and duration of cholesterol lowering and to assess the safety and tolerability of different dose regimens of LY3015014 in participants with high cholesterol. The study will also investigate how the body processes the drug and how the drug affects the body. Participants will remain on a stable diet and will continue taking cholesterol-lowering medications (statins with or without ezetimibe). After signing the informed consent document, the participant will complete a screening/run-in period that will last at most 8 weeks. Then, the treatment period will last approximately 16 weeks. After the treatment period, the participants will complete a follow-up period lasting approximately 8 weeks for a total study duration ranging from approximately 25 to 32 weeks.

开始日期2013-06-01

申办/合作机构

Eli Lilly & Co.

100 项与弗洛西单抗相关的临床结果

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100 项与弗洛西单抗相关的转化医学

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100 项与弗洛西单抗相关的专利（医药）

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6

项与弗洛西单抗相关的文献（医药）

2021-01-01·BioMed Research International3区 · 生物学

[Retracted] A Systematic Review and Meta‐Analysis of Therapeutic Efficacy and Safety of Alirocumab and Evolocumab on Familial Hypercholesterolemia

3区 · 生物学

ReviewOA

作者: Huang, Keke ; Yang, Huiyao ; Yu, Xin ; Zhu, Tiantian ; Xie, Shanshan ; Wan, Jinjin ; Zhang, Weifang ; Zeng, Hao ; Li, Juan ; Ge, Xiaoyue

Objectives. The aim of this study was to provide the first study to systematically analyze the efficacy and safety of PCSK9‐mAbs in the treatment of familial hypercholesterolemia (FH). Methods. A computer was used to search the electronic Cochrane Library, PubMed/MEDLINE, and Embase databases for clinical trials using the following search terms: “AMG 145”, “evolocumab”, “SAR236553/REGN727”, “alirocumab”, “RG7652”, “LY3015014”, “RN316/bococizumab”, “PCSK9”, and “familial hypercholesterolemia” up to November 2020. Study quality was assessed with the Cochrane Collaboration’s tool, and publication bias was evaluated by a contour‐enhanced funnel plot and the Harbord modification of the Egger test. After obtaining the data, a meta‐analysis was performed using R software, version 4.0.3. Results. A meta‐analysis was performed on 7 clinical trials (926 total patients). The results showed that PCSK9‐mAbs reduced the LDL‐C level by the greatest margin, WMD −49.14%, 95% CI: −55.81 to −42.47%, on FH versus control groups. PCSK9‐mAbs also significantly reduced lipoprotein (a) (Lp (a)), total cholesterol (TC), triglycerides (TG), apolipoprotein‐B (Apo‐B), and non‐high‐density lipoprotein cholesterol (non‐HDL‐C) levels and increased HDL‐C and apolipoprotein‐A1 (Apo‐A1) levels of beneficial lipoproteins. Moreover, no significant difference was found between PCSK9‐mAbs treatment and placebo in common adverse events, serious events, and laboratory adverse events. Conclusion. PCSK9‐mAbs significantly decreased LDL‐C and other lipid levels with satisfactory safety and tolerability in FH treatment.

2018-09-01·BMJ Open4区 · 医学

Impact of PCSK9 monoclonal antibodies on circulating hs-CRP levels: a systematic review and meta-analysis of randomised controlled trials

4区 · 医学

ReviewOA

作者: Cao, Ye-Xuan ; Liu, Hui-Hui ; Li, Sha ; Li, Jian-Jun

ObjectiveTo evaluate the potential effects of proprotein convertase subtilisin/kexin type 9 monoclonal antibody (PCSK9-mAb) on high-sensitivity C reactive protein (hs-CRP) concentrations.DesignA systematic review and meta-analysis of randomised controlled trials.Data sourcesPubMed, MEDLINE, the Cochrane Library databases, ClinicalTrials.gov and recent conferences were searched from inception to May 2018.Eligibility criteria for selecting studiesAll randomised controlled trials that reported changes of hs-CRP were included.ResultsTen studies involving 4198 participants were identified. PCSK9-mAbs showed a slight efficacy in reducing hs-CRP (−0.04 mg/L, 95% CI: −0.17 to 0.01) which was not statistically different. The results did not altered when subgroup analyses were performed including PCSK9-mAb types (alirocumab: 0.12 mg/L, 95% CI: −0.18 to 0.43; evolocumab: 0.00 mg/L, 95% CI: −0.07 to 0.07; LY3015014: −0.48 mg/L, 95% CI: −1.28 to 0.32; RG7652: 0.35 mg/L, 95% CI: −0.26 to 0.96), treatment duration (≤12w: 0.00 mg/L, 95% CI: −0.07 to 0.07; >12w: −0.11 mg/L, 95% CI: −0.45 to −0.23), participant characteristics (familial hypercholesterolaemia: 0.00 mg/L, 95% CI: −0.07 to 0.07; non-familial hypercholesterolaemia: 0.07 mg/L, 95% CI: −0.12 to 0.26; mix: −0.48 mg/L, 95% CI: −1.28 to 0.32) and treatment methods (monotherapy: 0.00 mg/L, −0.08 to 0.07; combination therapy: −0.08 mg/L, −0.37 to 0.21). Meta-regression analyses suggested no significant linear correlation between baseline age (p=0.673), sex (p=0.645) and low-density lipoprotein cholesterol reduction (p=0.339).ConclusionsOur updated meta-analysis suggested that PCSK9-mAbs had no significant impact on circulating hs-CRP levels irrespective of PCSK9-mAb types, participant characteristics and treatment duration or methods.

2017-02-17·mAbs2区 · 医学

Quantitative characterization of the mechanism of action and impact of a ‘proteolysis-permitting’ anti-PCSK9 antibody

2区 · 医学

Article

作者: Berna, Michael J. ; Beyer, Thomas P. ; Sperry, Andrea E. ; Wroblewski, Victor J. ; Schroeder, Krista M. ; Eacho, Patrick I. ; Hansen, Ryan J.

A recent report described a novel mechanism of action for an anti-proprotein convertase subtilisin-kexin type 9 (PCSK9) monoclonal antibody (LY3015014, or LY), wherein the antibody has improved potency and duration of action due to the PCSK9 epitope for LY binding. Unlike other antibodies, proteolysis of PCSK9 can occur when LY is bound to PCSK9. We hypothesized that this allowance of PCSK9 cleavage potentially improves LY efficiency through two pathways, namely lack of accumulation of intact PCSK9 and reduced clearance of LY. A quantitative modeling approach is necessary to further understand this novel mechanism of action. We developed a mechanism-based model to characterize the relationship between antibody pharmacokinetics, PCSK9 and LDL cholesterol levels in animals, and used the model to better understand the underlying drivers for the improved efficiency of LY. Simulations suggested that the allowance of cleavage of PCSK9 resulting in a lack of accumulation of intact PCSK9 is the major driver of the improved potency and durability of LY. The modeling reveals that this novel 'proteolysis-permitting' mechanism of LY is a means by which an efficient antibody can be developed with a total antibody dosing rate that is lower than the target production rate. We expect this engineering approach may be applicable to other targets and that the mathematical models presented herein will be useful in evaluating similar approaches.

100 项与弗洛西单抗相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D11398	-	-	DB15089

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
原发性高胆固醇血症	临床2期	丹麦	Eli Lilly & Co.	2013-06-01
原发性高胆固醇血症	临床2期	波兰	Eli Lilly & Co.	2013-06-01
原发性高胆固醇血症	临床2期	捷克	Eli Lilly & Co.	2013-06-01
原发性高胆固醇血症	临床2期	波多黎各	Eli Lilly & Co.	2013-06-01
原发性高胆固醇血症	临床2期	美国	Eli Lilly & Co.	2013-06-01
原发性高胆固醇血症	临床2期	加拿大	Eli Lilly & Co.	2013-06-01
原发性高胆固醇血症	临床2期	日本	Eli Lilly & Co.	2013-06-01
原发性高胆固醇血症	临床2期	荷兰	Eli Lilly & Co.	2013-06-01
高低密度脂蛋白胆固醇血症	临床2期	美国	Eli Lilly & Co.	2012-06-01

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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


NCT01618916 (CTgov)	临床1期	高低密度脂蛋白胆固醇血症	51	LY3015014 (1.0 mg/kg LY3015014 Q2W)	獵膚糧壓壓醖窪糧構窪(壓蓋鹹淵淵鏇遞繭廠蓋) = 壓鹽淵襯衊簾網憲簾範襯艱壓艱夢範壓鏇艱選 (鹽衊選壓憲鬱鑰觸壓鑰, 衊糧齋鬱餘夢觸壓築顧 ~ 糧積顧構鬱鹹顧淵遞憲) 更多	-	2019-02-25
				LY3015014 (1.0 mg/kg LY3015014 Q4W)	獵膚糧壓壓醖窪糧構窪(壓蓋鹹淵淵鏇遞繭廠蓋) = 選積獵獵觸壓範廠遞淵襯艱壓艱夢範壓鏇艱選 (鹽衊選壓憲鬱鑰觸壓鑰, 窪窪憲廠齋範製鬱鏇簾 ~ 醖憲鹽獵糧窪簾廠齋鹽) 更多
NCT01671085 (CTgov)	临床1期	高胆固醇血症	13	Placebo	(願構艱鑰鏇鑰膚窪製衊) = 鏇鏇遞遞觸獵齋膚艱遞壓選夢夢範膚糧範襯鹽 (獵艱壓繭遞鬱繭鬱範願, 遞蓋憲鹽膚壓糧醖構醖 ~ 簾憲網鹽膚廠鬱觸鹹鬱) 更多	-	2019-02-25
NCT01890967 (CTgov)	临床2期	原发性高胆固醇血症	527	Placebo+Ezetimibe+Statin (Placebo Q4W)	範構鬱淵構製網齋鹽襯(壓願衊鏇繭積觸衊廠製) = 齋選窪獵繭淵窪窪醖範艱選壓積淵艱鑰壓廠壓 (網遞鏇願襯夢網顧鹹網, 構鹽鑰繭網遞選壓遞窪 ~ 鹽選築餘淵選繭膚鏇蓋) 更多	-	2017-06-21
				LY3015014+Ezetimibe+Statin (20 mg LY3015014 Q4W)	範構鬱淵構製網齋鹽襯(壓願衊鏇繭積觸衊廠製) = 網鏇遞廠網築夢膚願觸艱選壓積淵艱鑰壓廠壓 (網遞鏇願襯夢網顧鹹網, 衊選膚壓蓋鹽選築鹹憲 ~ 積觸顧簾壓構築範鬱遞) 更多