Current and Next Steps Toward Prediction of Human Dose for Gene Therapy Using Translational Dose-Response Studies

被引：14

作者：

Aksenov, Sergey ^{[1
]}

Roberts, John C. ^{[2
]}

Mugundu, Ganesh ^{[3
]}

Mueller, Karen Thudium ^{[4
]}

Bhattacharya, Indranil ^{[5
]}

Tortorici, Michael A. ^{[2
]}

机构：

[1] Novartis Inst BioMed Res, Early Dev Analyt, Cambridge, MA USA

[2] CSL Behring, Clin Pharmacol & Pharmacometr, King Of Prussia, PA 19406 USA

[3] Takeda Pharmaceut Int Co, Cell Therapy Pharmacol & Modeling, Cambridge, MA USA

[4] GentiBio, Translat Sci, Cambridge, MA USA

[5] Takeda Pharmaceut Int Co, Quantitat Clin Pharmacol, Cambridge, MA USA

来源：

CLINICAL PHARMACOLOGY & THERAPEUTICS | 2021年 / 110卷 / 05期

关键词：

FACTOR-IX; ANGIOGENESIS; LIMITATIONS; HEMOPHILIA; DISEASE; LIVER;

D O I：

10.1002/cpt.2374

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Establishing dose response relationships is foundational in drug development. To improve confidence in a development program, understanding dose response in animals and how that translates to early clinical development studies is critical. Traditional approaches to predict clinical doses that achieve minimal biological activity and maintain wide safety margins may not apply to gene therapy (GT) because of differences in biological mechanisms of drug disposition and pharmacological activity when compared with more established drug modalities.

引用

页码：1176 / 1179

页数：4

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