TGF-alpha/epiregulin monoclonal antibody(Eli Lilly)(TGF-alpha/epiregulin monoclonal antibody(Eli Lilly))

概要

基本信息

药物类型

单克隆抗体

别名

EPIREG/TGFa MAB、Fepixnebart

+ [2]

靶点

EREG x TGF-α

作用机制

EREG抑制剂(表皮调节素抑制剂)、TGF-α抑制剂(转化生长因子α抑制剂)

治疗领域

神经系统疾病内分泌与代谢疾病皮肤和肌肉骨骼疾病+ [1]

在研适应症-

非在研适应症

慢性疼痛糖尿病肾病糖尿病周围神经性疼痛+ [2]

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-

序列信息

Sequence Code 126428H

来源: *****

Sequence Code 126431L

来源: *****

关联

6

项与 TGF-alpha/epiregulin monoclonal antibody(Eli Lilly) 相关的临床试验

NCT04529096 / Completed临床2期

Randomized, Placebo-Controlled, Phase 2 Clinical Trial to Evaluate LY3016859 for the Treatment of Chronic Low Back Pain

This study is being done to test the safety and efficacy of the study drug LY3016859 for the treatment of chronic low back pain. This trial is part of the chronic pain master protocol H0P-MC-CPMP (NCT05986292) which is a protocol to accelerate the development of new treatments for chronic pain.

开始日期2020-08-25

申办/合作机构

Eli Lilly & Co.

NCT04476108 / Completed临床2期

Randomized, Placebo-Controlled, Phase 2 Clinical Trial to Evaluate LY3016859 for the Treatment of Diabetic Peripheral Neuropathic Pain

This study is being done to test the safety and efficacy of the study drug LY3016859 for the treatment of diabetic peripheral neuropathic pain. This trial is part of the chronic pain master protocol H0P-MC-CPMP (NCT05986292) which is a protocol to accelerate the development of new treatments for chronic pain.

开始日期2020-07-15

申办/合作机构

Eli Lilly & Co.

NCT04456686 / Completed临床2期

Randomized, Placebo-Controlled, Phase 2 Clinical Trial to Evaluate LY3016859 for the Treatment of Osteoarthritis

This study is being done to test the safety and efficacy of LY3016859 for the treatment of osteoarthritis pain. This trial is part of the chronic pain master protocol H0P-MC-CPMP (NCT05986292) which is a protocol to accelerate the development of new treatments for chronic pain.

开始日期2020-07-01

申办/合作机构

Eli Lilly & Co.

100 项与 TGF-alpha/epiregulin monoclonal antibody(Eli Lilly) 相关的临床结果

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100 项与 TGF-alpha/epiregulin monoclonal antibody(Eli Lilly) 相关的转化医学

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100 项与 TGF-alpha/epiregulin monoclonal antibody(Eli Lilly) 相关的专利（医药）

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3

项与 TGF-alpha/epiregulin monoclonal antibody(Eli Lilly) 相关的文献（医药）

2018-09-01·Clinical Pharmacology in Drug Development4区 · 医学

Evaluation of the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy After Single and Multiple Dosings of LY3016859 in Healthy Subjects and Patients With Diabetic Nephropathy

4区 · 医学

Article

作者: Eli, Michelle ; Raddad, Eyas ; Deeg, Mark A. ; Flynt, Amy ; Sloan‐Lancaster, Joanne ; Tumlin, James

AbstractTwo phase 1 studies (TGAA and TGAB) evaluated the safety, pharmacokinetics, pharmacodynamics, and efficacy of LY3016859 (LY), a monoclonal antibody that binds epiregulin and transforming growth factor α (TGF‐α), administered intravenously or subcutaneously. In TGAA, 56 healthy subjects received a single dose of LY (0.1–750 mg intravenously, 50 mg subcutaneously) or placebo. In TGAB part A, 15 patients with diabetic nephropathy (DN) received 2 doses of LY (10–750 mg intravenously) or placebo, and in TGAB part B, 45 patients with DN received 5 doses of LY (50–750 mg intravenously) or placebo. Pharmacokinetics, pharmacodynamics, anti‐LY antibodies, and change in proteinuria and albuminuria were evaluated. Single and multiple doses of LY administered 3 weeks apart were well tolerated. Pharmacokinetics were nonlinear in healthy subjects and patients with DN, indicating target‐mediated drug disposition. Epiregulin level increased in both studies, and TGF‐α levels increased in the TGAB study, consistent with target engagement; however, LY treatment did not significantly reduce proteinuria or albuminuria in patients with DN. There was no obvious effect of LY on the disease‐related biomarkers monocyte chemoattractant protein‐1, synaptopodin, or transferrin. Although LY administration resulted in a high frequency of anti‐LY antibodies, pharmacokinetics, target engagement, and efficacy were not impacted.

2016-11-01·Protein Science4区 · 生物学

Structural basis of selectivity and neutralizing activity of a TGFα/epiregulin specific antibody

4区 · 生物学

Article

作者: Boyles, Jeffrey S. ; Druzina, Zhanna ; Witcher, Derrick R. ; Atwell, Shane ; Heuer, Josef G.

AbstractRecent studies have implicated a role of the epidermal growth factor receptor (EGFR) pathway in kidney disease. Skin toxicity associated with therapeutics which completely block the EGFR pathway precludes their use in chronic dosing. Therefore, we developed antibodies which specifically neutralize the EGFR ligands TGFα (transforming growth factor‐alpha) and epiregulin but not EGF (epidermal growth factor), amphiregulin, betacellulin, HB‐EGF (heparin‐binding epidermal growth factor), or epigen. The epitope of one such neutralizing antibody, LY3016859, was characterized in detail to elucidate the structural basis for ligand specificity. Here we report a crystal structure of the LY3016859 Fab fragment in complex with soluble human TGFα. Our data demonstrate a conformational epitope located primarily within the C‐terminal subdomain of the ligand. In addition, point mutagenesis experiments were used to highlight specific amino acids which are critical for both antigen binding and neutralization, most notably Ala41, Glu44, and His45. These results illustrate the structural basis for the ligand specificity/selectivity of LY3016859 and could also provide insight into further engineering to alter specificity and/or affinity of LY3016859.

2014-05-01·Journal of Pharmacology and Experimental Therapeutics3区 · 医学

Generation and Activity of a Humanized Monoclonal Antibody That Selectively Neutralizes the Epidermal Growth Factor Receptor Ligands Transforming Growth Factor-αand Epiregulin

3区 · 医学

Article

作者: Josef G Heuer ; Derek D Yang ; Ramona J Petrovan ; Anja Stauber ; Robert L Johnson ; Amita Datta-Mannan ; Matthew D Breyer ; Bernice Ellis ; Catherine B Beidler ; Derrick R Witcher ; Elaine M Conner ; Jeffrey S Boyles ; Shaoyou Chu ; Shannon M Harlan

At least seven distinct epidermal growth factor (EGF) ligands bind to and activate the EGF receptor (EGFR). This activation plays an important role in the embryo and in the maintenance of adult tissues. Importantly, pharmacologic EGFR inhibition also plays a critical role in the pathophysiology of diverse disease states, especially cancer. The roles of specific EGFR ligands are poorly defined in these disease states. Accumulating evidence suggests a role for transforming growth factor α (TGFα) in skin, lung, and kidney disease. To explore the role of Tgfa, we generated a monoclonal antibody (mAb41) that binds to and neutralizes human Tgfa with high affinity (KD = 36.5 pM). The antibody also binds human epiregulin (Ereg) (KD = 346.6 pM) and inhibits ligand induced myofibroblast cell proliferation (IC50 values of 0.52 and 1.12 nM for human Tgfa and Ereg, respectively). In vivo, a single administration of the antibody to pregnant mice (30 mg/kg s.c. at day 14 after plug) or weekly administration to neonate mice (20 mg/kg s.c. for 4 weeks) phenocopy Tgfa knockout mice with curly whiskers, stunted growth, and expansion of the hypertrophic zone of growth plate cartilage. Humanization of this monoclonal antibody to a human IgG4 antibody (LY3016859) enables clinical development. Importantly, administration of the humanized antibody to cynomolgus monkeys is absent of the skin toxicity observed with current EGFR inhibitors used clinically and no other pathologies were noted, indicating that neutralization of Tgfa could provide a relatively safe profile as it advances in clinical development.

100 项与 TGF-alpha/epiregulin monoclonal antibody(Eli Lilly) 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
腰痛	临床2期	波多黎各	Eli Lilly & Co.	2020-08-25
糖尿病周围神经性疼痛	临床2期	美国	Eli Lilly & Co.	2020-07-15
糖尿病周围神经性疼痛	临床2期	波多黎各	Eli Lilly & Co.	2020-07-15
慢性疼痛	临床2期	美国	Eli Lilly & Co.	2020-07-01
骨关节炎	临床2期	美国	Eli Lilly & Co.	2020-07-01
糖尿病肾病	临床2期	保加利亚	Eli Lilly & Co.	2013-03-01
糖尿病肾病	临床2期	美国	Eli Lilly & Co.	2013-03-01
腰痛	临床1期	美国	Eli Lilly & Co.	2020-08-25
慢性疼痛	临床前	波多黎各	Eli Lilly & Co.	2020-07-01

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临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT04476108 (CTgov)	临床2期	慢性疼痛 \| 糖尿病周围神经性疼痛	125	LY3016859 (750 Mg-500 mg LY3016859)	選鏇壓觸窪鏇願醖鑰築(壓壓蓋構獵鹽製壓獵積) = 簾觸艱醖願淵獵範繭範顧鏇憲糧製壓艱艱選網 (網廠遞糧鏇衊觸遞夢糧, 構蓋醖淵膚壓鏇醖壓壓 ~ 夢繭夢淵構蓋願繭廠築) 更多	-	2022-08-03
				Placebo (Placebo)	選鏇壓觸窪鏇願醖鑰築(壓壓蓋構獵鹽製壓獵積) = 繭遞繭餘憲顧憲範艱網顧鏇憲糧製壓艱艱選網 (網廠遞糧鏇衊觸遞夢糧, 範積窪繭廠顧範遞鑰壓 ~ 襯壓鏇憲醖艱積餘觸鏇) 更多
NCT04456686 (CTgov)	临床2期	骨关节炎 \| 慢性疼痛	117	LY3016859 (750 Mg-500 mg LY3016859)	衊鏇獵鬱壓鏇淵鏇糧廠(鏇鏇憲襯夢衊選積夢艱) = 壓醖簾製鏇廠餘蓋遞齋鬱觸壓齋製鹽構醖願襯 (憲鬱願糧遞憲窪築願觸, 製廠餘鹽觸鏇積壓顧鏇 ~ 積觸衊鏇繭醖糧範簾獵) 更多	-	2022-06-23
				Placebo (Placebo)	衊鏇獵鬱壓鏇淵鏇糧廠(鏇鏇憲襯夢衊選積夢艱) = 壓鬱醖鬱餘夢鹽範築廠鬱觸壓齋製鹽構醖願襯 (憲鬱願糧遞憲窪築願觸, 餘網鏇製繭鏇壓廠鹹齋 ~ 淵顧艱襯網觸夢網淵範) 更多
NCT04529096 (CTgov)	临床2期	腰痛 \| 慢性疼痛	149	LY3016859 (750 Mg-500 mg LY3016859)	鹹遞蓋願醖鹹醖膚觸醖(鹹衊艱願糧醖蓋膚齋築) = 襯獵齋膚製鑰鏇遞築憲艱鑰壓餘範觸醖憲製糧 (鏇夢願糧糧鏇糧廠觸鬱, 觸窪網積構醖糧範醖選 ~ 遞遞願衊鬱膚簾夢遞夢) 更多	-	2022-06-23
				Placebo (Placebo)	鹹遞蓋願醖鹹醖膚觸醖(鹹衊艱願糧醖蓋膚齋築) = 鹹顧糧積獵窪製鬱鑰餘艱鑰壓餘範觸醖憲製糧 (鏇夢願糧糧鏇糧廠觸鬱, 襯蓋艱繭醖廠鏇襯襯蓋 ~ 壓淵蓋壓艱淵鹹遞糧餘) 更多
NCT01545583 (CTgov)	临床1期	-	56	Placebo (Placebo IV)	(蓋願鹹齋構製製廠繭廠) = 簾積構觸廠網衊廠積膚遞鑰憲鹽夢廠襯觸製鑰 (窪艱齋醖衊廠廠鏇醖夢, 糧範繭醖願獵鹹壓構夢 ~ 遞醖廠選醖糧網衊夢構) 更多	-	2018-07-19
				Placebo (Placebo SC)	(蓋願鹹齋構製製廠繭廠) = 選壓簾夢餘選膚觸糧選遞鑰憲鹽夢廠襯觸製鑰 (窪艱齋醖衊廠廠鏇醖夢, 遞淵窪築淵憲範夢簾築 ~ 夢鏇齋範蓋構鬱網積築) 更多
NCT01774981 (CTgov)	临床1/2期	糖尿病肾病	60	Placebo (Placebo (Part B))	廠艱顧獵鬱獵選鏇獵獵(廠蓋鹽鑰襯蓋壓醖選壓) = 齋蓋積鑰鑰選願淵網獵鹹壓蓋遞夢鏇齋艱構鏇 (廠鑰襯夢顧鏇觸夢餘窪, 築顧糧遞襯願餘衊夢蓋 ~ 膚鏇窪製範憲膚獵獵選) 更多	-	2017-08-15
				LY3016859 (50 mg LY3016859 (Part B))	廠艱顧獵鬱獵選鏇獵獵(廠蓋鹽鑰襯蓋壓醖選壓) = 製鹹觸顧壓簾構窪構憲鹹壓蓋遞夢鏇齋艱構鏇 (廠鑰襯夢顧鏇觸夢餘窪, 齋鹹遞憲願獵繭獵窪憲 ~ 淵衊衊鑰壓選膚築廠淵) 更多