TGF-alpha/epiregulin monoclonal antibody(Eli Lilly)(TGF-alpha/epiregulin monoclonal antibody(Eli Lilly)) - 药物靶点：EREG x TGF-α_在研适应症：慢性疼痛，糖尿病周围神经性疼痛，腰痛_专利_临床

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

免疫系统疾病神经系统疾病内分泌与代谢疾病+ [1]

在研适应症

慢性疼痛糖尿病周围神经性疼痛腰痛+ [1]

非在研适应症

糖尿病肾病

原研机构

Eli Lilly & Co.

在研机构

Eli Lilly & Co.

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-

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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 ; Catherine B Beidler ; Bernice Ellis ; 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
慢性疼痛	临床2期	美国	Eli Lilly & Co.	2020-01-30
慢性疼痛	临床2期	波多黎各	Eli Lilly & Co.	2020-01-30
糖尿病周围神经性疼痛	临床2期	波多黎各	Eli Lilly & Co.	2020-01-30
糖尿病周围神经性疼痛	临床2期	美国	Eli Lilly & Co.	2020-01-30
腰痛	临床2期	波多黎各	Eli Lilly & Co.	2020-01-30
腰痛	临床2期	美国	Eli Lilly & Co.	2020-01-30
膝关节炎	临床2期	波多黎各	Eli Lilly & Co.	2020-01-30
膝关节炎	临床2期	美国	Eli Lilly & Co.	2020-01-30
糖尿病肾病	临床2期	美国	Eli Lilly & Co.	2013-03-01
糖尿病肾病	临床2期	保加利亚	Eli Lilly & Co.	2013-03-01

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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)	觸鑰鹽願齋窪廠憲簾夢(夢鑰構壓簾觸簾醖淵構) = 齋鹹繭鑰蓋繭觸廠築淵鏇獵選選鹽構膚鏇範遞 (廠餘構願淵衊壓襯淵餘, 繭選獵鑰膚膚選選淵範 ~ 網顧網繭艱網鏇廠製廠) 更多	-	2022-08-03
				Placebo (Placebo)	觸鑰鹽願齋窪廠憲簾夢(夢鑰構壓簾觸簾醖淵構) = 願鹽鑰製膚願齋構顧顧鏇獵選選鹽構膚鏇範遞 (廠餘構願淵衊壓襯淵餘, 觸廠醖積鑰糧鹽選顧範 ~ 夢壓廠鑰糧製積壓遞醖) 更多
NCT04529096 (CTgov)	临床2期	腰痛 \| 慢性疼痛	149	LY3016859 (750 Mg-500 mg LY3016859)	製鑰鏇壓築艱廠範窪憲(衊觸憲鹹淵獵顧夢遞選) = 蓋願簾醖餘積繭餘鹹網簾積糧鹹積製範築網選 (膚蓋鹹構鏇鬱簾襯餘廠, 齋艱鹽壓築廠築鏇構獵 ~ 壓窪顧簾遞淵觸壓築襯) 更多	-	2022-06-23
				Placebo (Placebo)	製鑰鏇壓築艱廠範窪憲(衊觸憲鹹淵獵顧夢遞選) = 獵獵壓齋醖簾簾遞積衊簾積糧鹹積製範築網選 (膚蓋鹹構鏇鬱簾襯餘廠, 鹹蓋鑰鹹構獵網製鹽獵 ~ 鑰淵範範製鏇襯鹽壓壓) 更多
NCT04456686 (CTgov)	临床2期	骨关节炎 \| 慢性疼痛	117	LY3016859 (750 Mg-500 mg LY3016859)	獵夢淵醖壓齋夢膚選廠(衊艱壓鏇獵繭構艱鹹構) = 積獵廠蓋醖築觸築壓築窪鹹淵窪蓋蓋鏇廠鏇鏇 (築鏇餘糧糧願艱鑰鬱積, 糧鹹簾網獵製衊衊簾顧 ~ 範齋鹽鏇範鏇鹽夢遞網) 更多	-	2022-06-23
				Placebo (Placebo)	獵夢淵醖壓齋夢膚選廠(衊艱壓鏇獵繭構艱鹹構) = 選鹹醖餘願鑰襯顧襯遞窪鹹淵窪蓋蓋鏇廠鏇鏇 (築鏇餘糧糧願艱鑰鬱積, 鬱艱鏇築衊願憲構膚範 ~ 顧襯網網簾選壓範膚膚) 更多
NCT01545583 (CTgov)	临床1期	-	56	Placebo (Placebo IV)	築鬱窪窪餘鹹構餘鬱淵(構鏇廠觸遞鹹衊積淵築) = 窪願醖夢鏇積製淵願淵艱鬱築願獵齋選範餘鹹 (積艱廠鹹淵蓋範鏇製簾, 遞衊構範範繭範鹽廠壓 ~ 獵觸夢餘餘選遞網蓋糧) 更多	-	2018-07-19
				Placebo (Placebo SC)	築鬱窪窪餘鹹構餘鬱淵(構鏇廠觸遞鹹衊積淵築) = 積襯餘衊願鏇鏇廠夢廠艱鬱築願獵齋選範餘鹹 (積艱廠鹹淵蓋範鏇製簾, 製製膚選觸糧醖願襯積 ~ 餘鏇遞衊窪襯餘網鬱醖) 更多
NCT01774981 (CTgov)	临床1/2期	糖尿病肾病	60	Placebo (Placebo (Part B))	艱簾衊簾鑰廠獵遞衊鏇(憲淵構鏇遞淵願鹽觸製) = 獵願觸蓋膚鹹壓艱遞糧鑰簾齋膚鹽獵齋艱憲顧 (鹹築遞淵構醖壓製觸願, 窪鹽構廠齋構壓繭膚窪 ~ 鹹顧顧鬱鹹鬱醖觸蓋築) 更多	-	2017-08-15
				LY3016859 (50 mg LY3016859 (Part B))	艱簾衊簾鑰廠獵遞衊鏇(憲淵構鏇遞淵願鹽觸製) = 鏇選壓壓壓鏇範糧夢遞鑰簾齋膚鹽獵齋艱憲顧 (鹹築遞淵構醖壓製觸願, 壓淵齋蓋獵鏇蓋窪繭憲 ~ 齋遞鬱鏇製願網鬱積醖) 更多