A 26-Week (With 26 Week Extension) Randomized, Multi-Center, Double-Blind Phase 2 Study to Evaluate the Efficacy and Safety of XC001 Gene Therapy as an Adjunct to Coronary Artery Bypass Graft Surgery for Patients With Symptomatic Coronary Artery Disease With Left Ventricular Dysfunction at Risk for Incomplete Revascularization

This is a 26-week (with a 26-week extension) multicenter, randomized, double-blind, placebo-controlled Phase 2 study of XC001 versus placebo. Approximately 116 participants who have CAD and have been referred for revascularization by CABG and who have, according to assessment by stress imaging multiple myocardial segments that are substantially ischemic, and that are unlikely to be fully revascularized during CABG for technical reasons, including diffuse atherosclerosis, lack of conduits, or insufficient target vessels.
Patients will be randomized in a 1:1 to XC001 or placebo injections during the final stages of the CABG procedure. Patients will have a baseline CMR at day 4-6 post CABG and additional assessments in the primary study period will be performed on Day 14, and Weeks 4, 12, and 26, (and during the extension period at 52 weeks).

开始日期2025-08-27

申办/合作机构

Xylocor Therapeutics, Inc.

NCT07048808

/ Recruiting临床2期

Endocardial Delivery of XC001 Gene Therapy for Refractory Angina Coronary Treatment: A 26-Week (With 26 Week Extension) Phase 2b Randomized, Multi-Center, Double-Blind, Sham Controlled Study to Evaluate Efficacy and Safety

This is a two-part study, comprised of an initial open-label run-in phase (Part 1) in a subset of 3 subjects to provide first data regarding safety, and feasibility of the percutaneous endovascular catheter-facilitated intramyocardial delivery of XC001 in patients with RA due to obstructive CAD.
Part 1 of the study is comprised of 3 subjects with RA (CCS class II-IV) who will receive 4×1011 viral particles (vp) XC001. An Independent Data Monitoring Committee (IDMC), the committee will review safety and feasibility data and approval to commence enrollment in Part 2 of the study.
Part 2 is a randomized, double-blind, sham-procedure control study. Subjects with RA (CCS class II-IV) with no therapeutic options will be randomized 1:1 to either the treatment group with catheter delivery of 4×1011 vp XC001 (approximately N=53) or a sham procedure group (approximately N=53). It is estimated that approximately 106 subjects will be randomized to result in 100 evaluable subjects. All subjects enrolled in Part 1, as well as Part 2 will follow all screening and safety monitoring procedures for up to 12 months (Table 2), and will be included in the safety analysis of the study.

开始日期2025-06-24

申办/合作机构

Xylocor Therapeutics, Inc.

NCT01757223

/ Withdrawn临床1/2期IIT

Phase I/II Study, Administration of AdVEGF-All6A+, a Replication Deficient Adenovirus Vector Expressing a cDNA/Genomic Hybrid of Human Vascular Endothelial Growth Factor to the Ischemic Myocardium...

The proposed Phase I/II clinical trial will be used to determine the safety and toxicity of direct administration of the vector AdVEGF-All6A+ to the ischemic myocardium and to generate preliminary evidence regarding whether direct administration of AdVEGF-All6A+ to the ischemic myocardium will induce growth of collateral blood vessels and improve cardiac function. This is a three-part, multinational/multi-center, placebo controlled study.

开始日期2020-12-01

申办/合作机构

Weill Medical College of Cornell University

100 项与 Encoberminogene Rezmadenovec 相关的临床结果

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100 项与 Encoberminogene Rezmadenovec 相关的转化医学

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100 项与 Encoberminogene Rezmadenovec 相关的专利（医药）

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项与 Encoberminogene Rezmadenovec 相关的文献（医药）

2025-05-04·EXPERT OPINION ON INVESTIGATIONAL DRUGS

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

Review

作者: Wong, Alan ; Duckers, Eric ; Guddeti, Raviteja R. ; Answini, Geoffrey ; Dittrich, Howard C. ; Rudick, Steven ; Henry, Timothy D.

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 heparan sulfate 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.

2024-05-01·Circulation-Cardiovascular Interventions

Angiogenic Gene Therapy for Refractory Angina: Results of the EXACT Phase 2 Trial

Article

作者: Latter, David A. ; Dittrich, Howard C. ; Rosengart, Todd K. ; Peterson, Mark W. ; Burke, Christopher R. ; Bakaeen, Faisal G. ; Chaitman, Bernard R. ; Povsic, Thomas J. ; Traverse, Jay H. ; Sun, Benjamin C. ; Ohman, E. Magnus ; Koch, Gary G. ; Pepine, Carl J. ; DiCarli, Marcelo F. ; Nakamura, Kenta ; Kowalewski, Elaine ; Answini, Geoffrey A. ; Byrnes, Dawn G. ; Henry, Timothy D. ; Crystal, Ronald G. ; Williams, Adam R. ; Mokadam, Nahush A.

BACKGROUND::

XC001 is a novel adenoviral-5 vector designed to express multiple isoforms of VEGF (vascular endothelial growth factor) and more safely and potently induce angiogenesis. The EXACT trial (Epicardial Delivery of XC001 Gene Therapy for Refractory Angina Coronary Treatment) assessed the safety and preliminary efficacy of XC001 in patients with no option refractory angina.

METHODS::

In this single-arm, multicenter, open-label trial, 32 patients with no option refractory angina received a single treatment of XC001 (1×10 11 viral particles) via transepicardial delivery.

RESULTS::

There were no severe adverse events attributed to the study drug. Twenty expected severe adverse events in 13 patients were related to the surgical procedure. Total exercise duration increased from a mean±SD of 359.9±105.55 seconds at baseline to 448.2±168.45 (3 months), 449.2±175.9 (6 months), and 477.6±174.7 (12 months; +88.3 [95% CI, 37.1–139.5], +84.5 [95% CI, 34.1–134.9], and +115.5 [95% CI, 59.1–171.9]). Total myocardial perfusion deficit on positron emission tomography imaging decreased by 10.2% (95% CI, −3.1% to 23.5%), 14.3% (95% CI, 2.8%–25.7%), and 10.2% (95% CI, −0.8% to −21.2%). Angina frequency decreased from a mean±SD 12.2±12.5 episodes to 5.2±7.2 (3 months), 5.1±7.8 (6 months), and 2.7±4.8 (12 months), with an average decrease of 7.7 (95% CI, 4.1–11.3), 6.6 (95% CI, 3.5–9.7), and 8.8 (4.6–13.0) episodes at 3, 6, and 12 months. Angina class improved in 81% of participants at 6 months.

CONCLUSIONS::

XC001 administered via transepicardial delivery is safe and generally well tolerated. Exploratory improvements in total exercise duration, ischemic burden, and subjective measures support a biologic effect sustained to 12 months, warranting further investigation.

REGISTRATION::

URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04125732.

2024-01-01·Gene therapy

Safety and biodistribution of XC001 (encoberminogene rezmadenovec) gene therapy in rats: a potential therapy for cardiovascular diseases

Article

作者: Dittrich, Howard C ; Gianchetti, Albert ; Thorne, Barb ; Stewart, Duncan J ; Manza, Linda L ; Reinhardt, Rickey R ; Byrnes, Dawn

Adenovirus-mediated gene therapy holds promise for the treatment of cardiovascular diseases such as refractory angina. However, potential concerns around immunogenicity and vector dissemination from the target injected tissue require evaluation. This study was undertaken to evaluate the safety and biodistribution of XC001, a replication-deficient adenovirus serotype 5 vector expressing multiple isoforms of human vascular endothelial growth factor (VEGF), following direct administration into normal rat myocardium. Animals received the buffer formulation or increasing doses of XC001 (1 × 10⁷, 2.5 × 10⁸ or 2.5 × 10⁹ viral particles). Based on in-life parameters (general health, body weights, clinical pathology, serum cardiac troponin I, plasma VEGF, and gross necropsy), there were no findings of clinical concern. On Day 8, intramyocardial administration of XC001 was associated with dose-related, left ventricular myocardial inflammation at injection sites, resolving by Day 30. XC001 DNA was not detected in blood at any time but was present at Day 8 around the site of injection and to a much lesser extent in the spleen, liver, and lungs, persisting at low levels in the heart and spleen until at least Day 91. These findings demonstrate that intramyocardial injection of XC001 is supported for use in human studies.

项与 Encoberminogene Rezmadenovec 相关的新闻（医药）

2025-07-10

·Business Wire

First Patient Dosed in XyloCor Therapeutics’ Phase 2b EXACT-2 Trial Evaluating XC001 for the Treatment of Coronary Artery Disease

KING OF PRUSSIA, Pa.--(BUSINESS WIRE)--XyloCor Therapeutics, a clinical-stage biopharmaceutical company focused on developing novel therapies for cardiovascular disease, announced the first patient has been dosed in the Phase 2b EXACT-2 trial, designed to evaluate its gene therapy candidate XC001 (encoberminogene rezmadenovec) in individuals with coronary artery disease and refractory angina. XC001 is an adenoviral vector-based gene therapy encoding for vascular endothelial growth factor (VEGF), uniquely designed as a one-time catheter-based treatment to reduce cardiac ischemia by creating new blood vessels in the heart and thereby reducing episodes of chest pain and improving patient ability to perform everyday activities. This percutaneous administration approach, injecting directly into the heart muscle, allows XC001 to achieve higher gene expression levels locally in the heart while minimizing systemic vector circulation and associated side effects. “Initiating the EXACT-2 trial is an important milestone as we continue to develop XC001 for the treatment of refractory angina in patients who have exhausted available treatment options and have a debilitating quality of life,” said Albert Gianchetti, President and CEO of XyloCor. “Building on the positive results from EXACT-1, we are now focused on advancing the EXACT-2 trial to bring this potentially transformative treatment to patients as quickly as possible.” EXACT-2 is a Phase 2b, multicenter, randomized, double-blind study in 100 patients with refractory angina to evaluate the safety and efficacy of a one-time gene therapy with XC001, delivered using the Extroducer® Infusion Catheter System, an endocardial delivery catheter designed to inject advanced therapies directly into the heart in a simple injection procedure in the cardiac catheterization lab. Additional information can be found here. The first patient was dosed by Timothy Henry, MD, at The Christ Hospital Health Network in Cincinnati, OH. “After seeing the convincing results from the EXACT-1 trial, we were eager to participate in EXACT-2,” commented Dr. Timothy Henry, a cardiovascular interventionist and the Lindner Family Distinguished Chair in Clinical Research and Medical Director of The Carl and Edyth Lindner Center for Research at The Christ Hospital. “We believe that XC001 delivered through the Extroducer® Infusion Catheter System will maintain the accuracy of delivery of XC001 to the heart and improve the safety over the surgical administration approach used in EXACT-1.” The XC001 Phase 1/2 EXACT-1 trial results supported the transformative, disease-modifying potential of XC001 to reduce cardiac ischemia, reduce anginal symptoms and improve the quality ‑of ‑life for cardiac patients who have no other treatment options. The results demonstrated the potential for XC001 to be safely administered and achieve durable clinical improvements, including increases in exercise duration, decrease in ischemic burden as measured by Positron Emission Tomography (PET) imaging and a reduction in angina frequency. Notably, 93% of patients in the trial entered with chest pain so severe that it markedly limited daily activities, whereas at six months 43% reported no chest pain with ordinary activities. XC001 was well tolerated in the patient population and there were no serious adverse events related to the study drug. XyloCor is also initiating a second clinical trial this year – a double-blind Phase 2 trial of XC001 as an adjunctive treatment to coronary artery bypass graft surgery (CABG). About XC001 XC001 is designed to reduce cardiac ischemia by creating new blood vessels in the heart that will bypass diseased blood vessels and improve blood flow. By restoring blood flow, chest pain associated with refractory angina may decrease, potentially improving patients’ quality of life by enabling them to engage in daily physical activities that would otherwise cause pain. XC001 is designed to avoid toxicity issues observed with other gene therapies through a strategy of one-time, local administration and delivery through an adenoviral vector. This approach allows XC001 to achieve higher gene expression in the heart while minimizing systemic vector circulation and associated side effects. About Extroducer® Infusion Catheter System The Extroducer® Infusion Catheter System is a first-in-class endovascular delivery device which enables direct-to-tissue drug delivery. The Extroducer® addresses a significant unmet need in the field of novel therapies, enabling targeted delivery of a wide range of treatment modalities to otherwise hard to reach tumors and organs. Using standard fluoroscopy equipment and routine interventional radiology approaches, the Extroducer provides access to hard-to-reach tissues by safely penetrating the vessel wall and delivering payload directly to the target location, or inside the heart ventricle. Smartwise received U.S. Food and Drug Administration (FDA) clearance under 510(k) for the Extroducer® delivery catheter in June 2022. In 2024, XyloCor entered into a licensing agreement with SmartWise, a unit of SmartCella, to deliver XC001 via the Extroducer® Infusion Catheter System. About Chronic Refractory Angina In the United States, coronary artery disease is a leading cause of death and disability. Chronic angina pectoris occurs when the heart muscle does not receive sufficient oxygen, resulting in chest pain. This is usually due to atherosclerotic plaques that block the coronary arteries. Refractory angina is a growing problem that occurs in patients with chronic angina who are symptomatic despite optimal medical therapy and are no longer eligible for mechanical interventions like percutaneous coronary intervention (PCI) and coronary artery bypass gracing (CABG). These patients currently have no treatment options and are frequently highly symptomatic, which severely impacts their quality of life, and may exacerbate comorbidities and cause further deterioration of their health status. Refractory angina results in significant consumption of healthcare resources, including visits to the emergency department as a result of patients’ chest pain. About XyloCor XyloCor Therapeutics, Inc. is a private, clinical-stage biopharmaceutical company developing potential best-in-class gene therapies to transform outcomes for patients with cardiovascular disease. The Company’s lead product candidate, XC001, is in clinical development for use in patients with coronary artery disease and refractory angina for whom there are no treatment options. XyloCor has a second preclinical investigational product, XC002, in the discovery stage, being developed for the treatment of patients with cardiac tissue damage from heart attacks. The company, which was co‑founded by Ronald Crystal, MD, and Todd Rosengart, MD, has an exclusive license from Cornell University. For more information, visit www.xylocor.com. About SmartCella SmartCella, founded in 2014, is a global biotech company pioneering the future of targeted therapies through delivery solutions and advanced therapy development. SmartCella combines novel delivery platforms, such as the Extroducer® (an endovascular delivery device that enables direct injection to hard-to-reach organs and tumors), with cutting-edge development and manufacturing of cell therapies. For more information, visit www.smartcella.com.

基因疗法引进/卖出临床2期临床结果

2025-05-15

·CPHI制药在线

金笔奖|浅谈心血管疾病药物创新图谱

关注并星标CPHI制药在线心血管疾病（CVD）作为全球范围内的首要致死因素，其治疗手段的革新始终是医学界关注的焦点。近年来，随着基因组学、分子生物学和药物递送技术的突破，心血管药物的研发正经历一场深刻的变革；从传统的单一靶点药物到基于基因编辑的精准治疗，从代谢调控到免疫调节的多维度干预，创新药物的开发不仅为患者提供了更多治疗选择，也重新定义了心血管疾病的管理模式。本文将围绕当前研发方向，结合临床试验数据、技术突破及产业动态，探讨心血管药物开发的现状、挑战与未来趋势。精准治疗与罕见病突破：ATTR-CM转甲状腺素蛋白淀粉样变性心肌病（ATTR-CM）由TTR蛋白异常沉积引发的心肌病变，曾因诊断困难且缺乏有效治疗手段导致极高死亡率；近年来，针对TTR蛋白稳定与清除的药物开发取得显著成果。辉瑞的Tafamidis作为首个获批的TTR稳定剂，通过维持四聚体结构抑制淀粉样纤维形成，其2024年前三季度销售额达39亿美元，印证了罕见病药物的巨大市场潜力；BridgeBio公司开发的Attruby凭借≥90%的TTR稳定率，在III期试验中将心血管死亡和住院风险降低34%，于2024年11月获FDA批准，进一步巩固了这一赛道的竞争格局。RNA靶向疗法的介入为ATTR-CM治疗提供了新维度。Alnylam公司的siRNA药物Amvuttra（vutrisiran）通过沉默TTR mRNA显著减少淀粉样沉积，其针对ATTR-CM的适应症正处于FDA审查阶段。阿斯利康与Ionis合作的反义寡核苷酸疗法Wainua（eplontersen）则通过阻断TTR蛋白合成发挥作用，III期临床试验预计2026年完成。这些进展不仅凸显了基因沉默技术在心血管领域的应用潜力，也揭示了罕见病药物研发从单一机制向多途径联合干预的转变趋势。临床前研究表明，联合使用TTR稳定剂与清除剂可能更有效地延缓疾病进展，而新型生物标志物（如心脏MRI的T1 mapping技术）的普及使得早期诊断成为可能，从而大幅提升药物干预的窗口期。GLP-1受体激动剂的多维拓展最初作为糖尿病治疗药物开发的司美格鲁肽（Semaglutide），因在减重领域的显著效果引发全球关注，而其对心血管系统的保护作用更成为近年来的研究热点。2024年3月，诺和诺德基于SELECT试验数据，成功将司美格鲁肽的适应症扩展至心血管疾病合并肥胖患者的主要不良事件（MACE）风险降低，试验显示其可将MACE风险降低20%。这一突破不仅标志着GLP-1药物从代谢领域正式进军心血管核心治疗圈，更揭示了能量代谢与心血管病理机制的深层关联。礼来的替尔泊肽（Tirzepatide）作为GIP/GLP-1双受体激动剂，则进一步拓展了此类药物的应用边界。在针对射血分数保留型心衰（HFpEF）的III期试验中，替尔泊肽使患者呼吸困难与疲劳症状减轻38%，这一结果挑战了传统心衰治疗的药物设计逻辑——通过改善代谢紊乱而非直接增强心肌收缩力来实现症状缓解；这种机制创新为心衰治疗开辟了新路径，也引发学界对“代谢重构”概念的深入探讨。目前，安进公司开发的每月注射一次的双重激动剂MariTide已进入II期临床，其独特的长效设计有望解决患者依从性难题；而Structure Therapeutics的口服小分子GLP-1药物GSBR-1292则通过肝脏靶向递送系统降低胃肠道副作用，II期数据显示其减重效果与注射剂相当。基因与细胞疗法基因疗法的出现为遗传性心血管疾病提供了根治可能。以肥厚型心肌病（HCM）为例，约60%病例由MYH7或MYBPC3基因突变引起。Tenaya Therapeutics开发的TN-201通过AAV9载体递送截短的MYBPC3基因，补偿突变导致的蛋白功能缺失，其Ib/II期试验显示患者心肌肥厚指标稳定超过12个月。而Lexeo公司的LX2006针对弗里德赖希共济失调相关心肌病，通过递送FXN基因恢复线粒体功能，I/II期试验中患者的NT-proBNP水平下降42%，为遗传性心肌病的基因修复提供了直接证据。在心力衰竭领域，基因疗法的应用更趋多元化。Renova Therapeutics的RT-100通过腺病毒载体过表达腺苷酸环化酶6（AC6），增强心肌细胞cAMP信号通路，II期试验中患者左心室射血分数（LVEF）提升5.2%。XyloCor公司的XC001则通过VEGF基因递送促进心肌血管新生，在难治性心绞痛患者中实现运动耐受时间延长30%。这些疗法开始突破单基因修复的局限，转向多通路协同调控。例如，Regenxbio的RGX-202针对杜氏肌营养不良心肌病，通过微抗肌萎缩蛋白基因治疗，在儿童患者中实现46%-77%的蛋白表达，同时抑制TGF-β通路以减少心肌纤维化；这种多靶点设计策略显著提高了治疗效果，但也对载体递送效率和安全性提出更高要求。RNA医学的崛起RNA靶向疗法的精准特性使其在心血管领域崭露头角。脂蛋白(a) [Lp(a)] 作为动脉粥样硬化的独立风险因子，传统药物难以有效干预。恒瑞医药与默沙东合作开发的HRS-5346作为首款口服Lp(a)小分子抑制剂，通过结合载脂蛋白(a)的kringle IV-2结构域抑制其组装，临床前研究显示可使Lp(a)水平降低80%，这一突破不仅可能改写动脉粥样硬化防治策略，更验证了RNA层面干预的可行性。非编码RNA（ncRNA）的调控则为心衰治疗提供了新思路。诺和诺德收购Cardior Pharmaceuticals后推进的CDR132L，通过抑制miR-132逆转心肌纤维化进程。II期试验HF-REVERT中，280名慢性心衰患者接受治疗后LVEF提升4.3%，且心脏胶原蛋白标志物PIIINP下降15%。Cardior开发的ncRNA平台可同时靶向miR-132、miR-208a等多个调控节点，这种多通路协同作用模式有望克服传统单靶点药物的局限性。传统药物的新发现：麻醉剂的心脏保护效应围术期心血管并发症的防治需求，意外催生了麻醉药物的心脏保护机制研究。丙泊酚作为常用静脉麻醉剂，其抗氧化特性通过激活Nrf2通路抑制再灌注损伤，动物实验显示可使心肌梗死面积减少38%。七氟烷的线粒体保护作用则与KATP通道开放相关，临床研究证实其可降低冠状动脉搭桥术后患者肌钙蛋白峰值水平。而右美托咪定通过抑制NF-κB通路减轻全身炎症反应，同时延长心脏舒张期改善冠脉灌注，使高危手术患者的心血管事件发生率降低22%。这些发现不仅拓展了传统药物的应用场景，也为心脏保护剂的开发提供了新的分子靶点。挑战与未来方向尽管创新浪潮汹涌，心血管药物开发仍面临多重挑战。基因疗法百万美元级的定价与长期安全性问题制约其普及，需探索风险分担保险与递送系统优化策略，RNA药物的脱靶效应和肝脏富集特性要求更精准的靶向技术。未来，心血管治疗将向疾病修饰（disease modification）方向演进，早期干预与多靶点协同成为核心策略，而合成生物学与时空组学技术或将重新定义药物设计范式。参考文献：［1］Liu, M., & Zhang, Y. H.(2013). 常见温热药在心血管疾病治疗中的应用概况 [Application of common warm-natured drugs in the treatment of cardiovascular diseases]. 湖北中医杂志, 29(6), 149–150. ［2］Zhou, C. Y., & Cao, M. J.(2023). RNA沉默在柑桔裂皮类病毒与树皮裂纹类病毒拮抗中的作用 [Effects of RNA silencing during antagonism between citrus exocortis viroid and citrus bark cracking viroid]. Molecular Plant Pathology, 24(7), 1023-1035. ［3］中国心血管健康与疾病报告2023概要 [2023 report on cardiovascular health and diseases in China]. 中华心血管病杂志, 51(8), 723–740.作者简介：@Ethan，制药工程背景，就职于某制药企业，将所学知识与实践紧密结合，致力于药品生产、质量控制与技术创新等。END【企业推荐】领取CPHI & PMEC China 2025展会门票来源：CPHI制药在线声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。投稿邮箱：Kelly.Xiao@imsinoexpo.com▼更多制药资讯，请关注CPHI制药在线▼点击阅读原文，进入智药研习社~

寡核苷酸siRNA信使RNA基因疗法临床3期

2025-03-23

·药通社

盘点：创新心血管药物开发热点

注：本文不构成任何投资意见和建议，以官方/公司公告为准。随着 BridgeBio 的Attruby 最近在转甲状腺素蛋白淀粉样变性心肌病（ATTR-CM）中的获批，心血管药物开发领域正在经历一场复兴。据预测心血管药物市场预计将从 2024 年的约 1500 亿美元增长到 2033 年的 2070 亿美元。从辉瑞和诺华等大型制药公司到包括 BridgeBio 和 Regenxbio 在内的小型生物技术公司，很对公司都在开发心血管新药，以期在增长的市场中分一杯羹。本文盘点了近年来心血管新药的开发热点。 ATTR-CM治疗药物：转甲状腺素蛋白淀粉样变心肌病（ATTR-CM）是由不稳定转甲状腺素蛋白（TTR）沉积于心肌间质导致限制性心肌病和进行性心力衰竭。ATTR-CM发病率估计不到1%，为罕见病，缺乏早期诊断的方法和有效的治疗措施，严重影响了患者的生活质量并危及生命。预计到 2030 年，该疾病市场将达到 93.5 亿美元。药物：Tafamidis 企业：辉瑞 Vyndaqel（tafamidis meglumine）和Vyndamax（tafamidis）2019年5月初获得FDA批准，成为首个治疗ATTR-CM的药物。之后相继在欧盟、中国等获批。该药通过结合 TTR 四聚体并抑制解离为能够在心脏组织中变性和沉积的单体，从而抑制甲状腺素蛋ATTR-CM的进展。根据辉瑞财报，2021-2023年Tafamidis全球销售额分别为20.15、24.47、33.21亿美元，2024年前9个月，Tafamidis产品销售额已达39.07亿美元。药物：Attruby 企业：BridgeBio 2024年11月，FDA批准了Attruby用于治疗患有转甲状腺素蛋白淀粉样变性心肌病（ATTR-CM）的成年人，以减少心血管死亡和心血管相关的住院治疗。其主要作用机制是通过结合转甲状腺素蛋白的甲状腺素结合位点，减少转甲状腺素蛋白（TTR）四聚体分解为其组成单体的速度，从而抑制由此引发的淀粉样变性过程。Attruby是第一个也是唯一一个药物标签上标明转甲状腺素蛋白（TTR）接近完全稳定（≥90％）的药物。 Attruby的批准得到了III期ATTRibute-CM的积极结果的支持，其显著减少了死亡和心血管相关的住院，并改善了生活质量。预期该药2028年销售额可达10亿美元。药物：Amvuttra（vutrisiran）企业：Alnylam Amvuttra是一种双链小干扰RNA（siRNA），能够靶向并沉默特定的信使RNA（mRNA），在突变型和野生型转甲状腺素（TTR）制造出来之前进行阻断，减少TTR淀粉样蛋白在组织中的沉积，促进组织中沉积的TTR淀粉样蛋白的清除，并恢复这些组织的功能。Amvuttra 已被批准用于治疗遗传性转甲状腺素蛋白介导的（hATTR）淀粉样变性多发性神经病。目前，FDA 已接受其在 ATTR-CM 中审查，审批决定日期为 3 月 23 日。此外，在 ATTR-CM 领域竞争的还有阿斯利康和 Ionis Pharmaceuticals，他们正在合作开发反义 RNA 沉默疗法 Wainua （eplontersen）。与 Amvuttra 一样，Wainua 被批准用于治疗 hATTR 淀粉样变性。该候选药物目前正在 III 期 CARDIO-TTRansform 研究中进行研究ATTR-CM，结果预计将于 2026 年公布。 GLP-1药物： GLP-1 激动剂是生物制药公司最热门的商品，除了肥胖、糖尿病和其他适应症外，在心血管疾病方面也取得了进展。药物：Wegovy（索马鲁肽）公司：诺和诺德 2024 年 3 月，FDA 批准了Wegovy（索马鲁肽）的标签扩展，以降低患有心血管疾病和肥胖或超重的成年人患心血管死亡、心脏病发作和中风的风险。这使得司美格鲁肽成为首款获批用于辅助患有心血管疾病及肥胖或超重的成年人预防重大心血管事件的减重药物。司美格鲁肽针对心血管疾病新适应证的疗效和安全性在一项Select多中心、安慰剂对照的双盲试验中获得证实，针对1.76万名受试者的随机对照分析试验显示，司美格鲁肽显著降低了主要不良心血管事件（包含心血管死亡、心脏病发作和中风）的风险，接受司美格鲁肽的受试者中发生此类事件的比例为6.5%，而安慰剂组中这一比例为8%。药物：tirzepatide 公司：礼来替尔泊肽（tirzepatide）是礼来公司研发并成功上市的一种新型的GIP/GLP-1双受体激动剂，在2022年获批治疗糖尿病后，又于2023年11月在美国获得减肥批准。 2024年8月1日，礼来还宣布其Zepbound在Ⅲ期治疗肥胖伴射血分数保留型心力衰竭（HFpEF）研究中取得成功。SUMMIT 结果显示，与安慰剂相比，tirzepatide 在两个主要终点方面均表现出统计学上显着的改善，该药物显著减轻了患者心力衰竭症状（38%）其中包括呼吸急促、疲劳和心律不齐。此外，安进公司最近发布了 MariTide 的 II 期数据，MariTide 是每月一次GIP/GLP-1双受体激动剂。安进公司正在推动 MariTide 在心血管和其他适应症的后期开发。 2024年12月，Structure启动了其口服 GLP-1R 选择性小分子的 IIb 期剂量递增研究。除了减肥终点外，该公司还关注心血管益处的指标，收集有关血脂、血压和代谢控制的数据，作为其为期 36 周的研究结束时的探索性数据。心血管疾病基因疗法药物：RT-100 企业：Renova Therapeutics RT-100 是 Renova 正在开发的用于充血性心力衰竭（CHF）的基因疗法。RT-100 通过传递 AC6 基因的副本起作用，该基因编码一种在心肌中发现的、对调节心脏功能起着核心作用的蛋白质，从而提高心脏中 AC6 蛋白的含量，改善器官的功能。截至 2024 年 5 月，Renova 正准备向 FDA提交其关键的 IIb/III 期研究计划。药物：XC001 企业：XyloCor Therapeutics XC001 靶向慢性难治性心绞痛， XC001通过将 VEGF 基因的拷贝输送到心脏，促进新血管的发育并恢复心肌中健康的氧气水平。 2024 年 5 月，XyloCor 发布了其I/II 期 EXACT 临床试验 II 期部分的结果，证明该基因疗法是安全的，可显著改善患者的运动持续时间、心绞痛频率和胸痛。药物：RGX-202 公司：Regenxbio RGX-202是针对杜氏肌营养不良症（DMD）中的心肌病的一次性治疗方法。 RGX-202通过递送微抗肌萎缩蛋白转基因起作用，该转基因编码带有 C 端结构域的氨基酸链的抗肌萎缩蛋白，有助于使心肌更加强壮。 2024 年 8 月，Regenxbio 报告了I/II 期试验的中期数据，称 5.8 岁和 8.5 岁患者的微抗肌萎缩蛋白表达分别为 77.2% 和 46.5%。药物：AB-1002 公司：AskBio AskBio公司的 AB-1002 是一种一次性基因疗法，旨在提高心脏中特定蛋白质抑制剂的表达，用于治疗充血性心力衰竭。 2023 年 11 月， AB-1002 的早期 I期数据显示在 12 个月的随访中，单剂量治疗三名患者的左心室射血分数和症状具有临床意义的改善，运动功能也有所改善。目前AB-1002 正在进行 II 期 GenePHIT 研究。药物：TN-201 公司：Tenaya Therapeutics TN-201是一种使用腺相关病毒载体并靶向 MYBPC3 基因突变的基因疗法，用于治疗肥厚型心肌病。 TN-201的早期 Ib/II 期数据表明在接受治疗后，患者在心脏组织中显示出可检测的载体 DNA 水平，以及转基因 RNA 表达的迹象，疾病的临床标志物也稳定或逐渐改善。药物：LX2006 公司：Lexeo Therapeutics LX2006是一种基于腺相关病毒（AAV）的基因疗法，旨在通过静脉注射递送功能性FXN基因来促进FXN蛋白的表达，并恢复心肌细胞中的线粒体功能。用于治疗弗里德赖希共济失调（FA）心肌病。在SUNRISE-FA临床1/2期试验和另一项1A期试验中期数据显示，该疗法耐受性良好，且多种肥厚性心脏生物标志物均有临床意义的改善。来源：药事纵横 ↓ 扫码加入交流群 ↓ 投稿/内容沟通：华籍美人（Ww_150525）推荐阅读

财报siRNA临床3期

100 项与 Encoberminogene Rezmadenovec 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
左心室功能不全	临床2期	美国	Xylocor Therapeutics, Inc.	2025-08-27
难治性心绞痛	临床2期	美国	Xylocor Therapeutics, Inc.	2025-06-24
心绞痛	临床2期	-	Weill Medical College of Cornell University	2020-12-01
缺血	临床2期	美国	Xylocor Therapeutics, Inc.	2020-01-24

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临床结果

适应症

分期

评价

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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


NCT04125732 (EXACT, ESC2023)	临床2期	难治性心绞痛	-	XC001 gene therapy	壓鑰構襯鏇鏇顧製製獵(獵遞蓋餘鹽鬱網網簾觸) = 觸鹽築壓糧繭蓋夢願糧選製範繭獵網窪憲廠憲 (願製選淵窪簾蓋餘鬱鹽, 31.3 ~ 139.7)	积极	2023-08-25
ASGCT2021	临床3期	难治性心绞痛 VEGF	-	XC001	淵選簾鏇範憲艱衊襯衊(網醖築鹽鹹淵繭繭顧衊) = vector-derived VEGF secreted by the cardiomyocytes was capable of stimulating a VEGF-responsive cell line similarly to control recombinant VEGF protein 顧繭築遞糧觸襯鏇醖憲 (淵襯壓窪積廠窪鬱願繭 ) 更多	-	2021-04-27
ASGCT2021	临床3期	难治性心绞痛 VEGF	-	XC001 (Human Cardiomyocyte Cell Lines)		-	2021-04-27