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

作者：Kenta Nakamura, Timothy D. Henry, Jay H. Traverse, David A. Latter, Nahush A. Mokadam, Geoffrey A. Answini, Adam Williams, Benjamin Sun, Christopher R. Burke, Faisal G. Bakaeen, Marcelo F. DiCarli, Bernard Chaitman, Mark W. Peterson, Dawn G. Byrnes, E. Magnus Ohman, Carl J. Pepine, Ronald G. Crystal, Todd K. Rosengart, Elaine K. Kowalewski, Gary G. Koch, Howard C. Dittrich, Thomas J. Povsic, on behalf of the EXACT Trial Investigators · 发表于：Circulation Cardiovascular Interventions · 年份：2024 · DOI：10.1161/circinterventions.124.014054 · 被引用次数：23 · 研究领域：Virus-based gene therapy research、Pain Management and Treatment、Ultrasound and Hyperthermia Applications

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: 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 exerci...