A VEGF gene therapy approach for the treatment of patients with coronary artery disease and refractory angina: assessment of clinical development.

IF 4.9 2区 医学 Q1 PHARMACOLOGY & PHARMACY
Raviteja R Guddeti, Alan Wong, Steven Rudick, Geoffrey Answini, Eric Duckers, Howard C Dittrich, Timothy D Henry
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引用次数: 0

Abstract

Introduction: Vascular endothelial growth factor (VEGF) gene therapy is a novel treatment strategy for refractory angina (RA) that works by promoting myocardial neoangiogenesis and collateral circulation formation. XC001 (encoberminogene rezmadenovec) is a novel, replication-deficient, non-integrating recombinant adenovirus vector formally referred to as AdVEGF-All6A+ engineered to produce three isoforms of VEGF A (121, 165, and 189) that are proven to induce neoangiogenesis and constructed specifically to increase the expression of VEGF 189 and 165 to improve safety because of its heparinsulfate binding domain.

Areas covered: We review the clinical development of XC001 and results of the EXACT (Epicardial delivery of encoberminogene rezmadenovec [XC001] gene therapy for refractory Angina Coronary Treatment) phase 1 and phase 2 trials.

Expert opinion: In initial trials, intramyocardial XC001 has been shown to be safe with signals for efficacy in decreasing myocardial perfusion defects, improving exercise duration, and anginal complaints in patients with RA. A Phase 2 trial using a novel percutaneous delivery catheter for endomyocardial delivery of XC001 is currently underway and has potential benefits in multiple other conditions, including as an adjunct therapy in patients undergoing CABG treatment at risk for incomplete revascularization, patients with coronary microvascular dysfunction, and others with peripheral arterial disease.

血管内皮生长因子基因治疗冠状动脉疾病和难治性心绞痛:临床进展评估
血管内皮生长因子(VEGF)基因治疗是一种新的治疗顽固性心绞痛(RA)的策略,其作用是促进心肌新生血管生成和侧支循环的形成。XC001 (encoberminogene rezmadenovec)是一种新型的、复制缺陷的、非整合的重组腺病毒载体,其正式名称为AdVEGF-All6A+,旨在产生三种VEGF a(121、165和189)的异构体,这些异构体已被证明可以诱导新血管生成,并且由于其肝磷脂结合结构域,专门用于增加VEGF 189和165的表达以提高安全性。涵盖领域:我们回顾了XC001的临床发展和EXACT(心外膜递送encoberminogene rezmadenovec [XC001]基因治疗难治性心绞痛冠状动脉治疗)一期和二期试验的结果。专家意见:在初步试验中,心肌内XC001已被证明是安全的,在减少心肌灌注缺陷、改善运动持续时间和RA患者的心绞痛症状方面具有有效的信号。目前正在进行一项使用新型经皮输送导管进行XC001心内膜输送的2期试验,该试验在多种其他情况下具有潜在的益处,包括作为CABG治疗中存在不完全血运重建风险的患者、冠状动脉微血管功能障碍患者和其他外周动脉疾病患者的辅助治疗。
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来源期刊
CiteScore
10.00
自引率
0.00%
发文量
71
审稿时长
6-12 weeks
期刊介绍: Expert Opinion on Investigational Drugs (ISSN 1354-3784 [print], 1744-7658 [electronic]) is a MEDLINE-indexed, peer-reviewed, international journal publishing review articles and original papers on drugs in preclinical and early stage clinical development, providing expert opinion on the scope for future development. The Editors welcome: Reviews covering preclinical through to Phase II data on drugs or drug classes for specific indications, and their potential impact on future treatment strategies Drug Evaluations reviewing the clinical and pharmacological data on a particular drug Original Research papers reporting the results of clinical investigations on agents that are in Phase I and II clinical trials The audience consists of scientists, managers and decision-makers in the pharmaceutical industry, and others closely involved in R&D.
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