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

Authors

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

Language

English

Publication Date

5-1-2024

Journal

Circulation: Cardiovascular Interventions

DOI

10.1161/CIRCINTERVENTIONS.124.014054

PMID

38696284

PMCID

PMC11097950

PubMedCentral® Posted Date

5-2-2024

PubMedCentral® Full Text Version

Post-print

Abstract

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 (1×1011 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.

Keywords

Humans, Male, Female, Middle Aged, Angina Pectoris, Genetic Therapy, Aged, Treatment Outcome, Neovascularization, Physiologic, Genetic Vectors, Vascular Endothelial Growth Factor A, Time Factors, Exercise Tolerance, Adenoviridae, Recovery of Function, angiogenesis, coronary artery disease, genetic therapy, positron emission tomography, vascular endothelial growth factor A

Comments

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

Published Open-Access

yes

Recommended Citation

Nakamura, Kenta; Henry, Timothy D; Traverse, Jay H; et al., "Angiogenic Gene Therapy for Refractory Angina: Results of the EXACT Phase 2 Trial" (2024). Faculty and Staff Publications. 4965.
https://digitalcommons.library.tmc.edu/baylor_docs/4965