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Long-term safety and efficacy of intramyocardial adenovirus-mediated VEGF-D(ΔNΔC) gene therapy eight-year follow-up of phase I KAT301 study

In phase I KAT301 trial, intramyocardial adenovirus-mediated vascular endothelial growth factor -D(ΔNΔC) (AdVEGF-D) gene therapy (GT) resulted in a significant improvement in myocardial perfusion reserve and relieved symptoms in refractory angina patients at 1-year follow-up without major safety con...

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Autores principales: Leikas, Aleksi J., Hassinen, Iiro, Hedman, Antti, Kivelä, Antti, Ylä-Herttuala, Seppo, Hartikainen, Juha E. K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9159942/
https://www.ncbi.nlm.nih.gov/pubmed/34593990
http://dx.doi.org/10.1038/s41434-021-00295-1
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author Leikas, Aleksi J.
Hassinen, Iiro
Hedman, Antti
Kivelä, Antti
Ylä-Herttuala, Seppo
Hartikainen, Juha E. K.
author_facet Leikas, Aleksi J.
Hassinen, Iiro
Hedman, Antti
Kivelä, Antti
Ylä-Herttuala, Seppo
Hartikainen, Juha E. K.
author_sort Leikas, Aleksi J.
collection PubMed
description In phase I KAT301 trial, intramyocardial adenovirus-mediated vascular endothelial growth factor -D(ΔNΔC) (AdVEGF-D) gene therapy (GT) resulted in a significant improvement in myocardial perfusion reserve and relieved symptoms in refractory angina patients at 1-year follow-up without major safety concerns. We investigated the long-term safety and efficacy of AdVEGF-D GT. 30 patients (24 in VEGF-D group and 6 blinded, randomized controls) were followed for 8.2 years (range 6.3–10.4 years). Patients were interviewed for the current severity of symptoms (Canadian Cardiovascular Society class, CCS) and perceived benefit from GT. Medical records were reviewed to assess the incidence of major cardiovascular adverse event (MACE) and other predefined safety endpoints. MACE occurred in 15 patients in VEGF-D group and in five patients in control group (21.5 vs. 24.9 per 100 patient-years; hazard ratio 0.97; 95% confidence interval 0.36–2.63; P = 0.95). Mortality and new-onset comorbidity were similar between the groups. Angina symptoms (CCS) were less severe compared to baseline in VEGF-D group (1.9 vs. 2.9; P = 0.006) but not in control group (2.2 vs. 2.6; P = 0.414). Our study indicates that intramyocardial AdVEGF-D GT is safe in the long-term. In addition, the relief of symptoms remained significant during the follow-up.
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spelling pubmed-91599422022-06-03 Long-term safety and efficacy of intramyocardial adenovirus-mediated VEGF-D(ΔNΔC) gene therapy eight-year follow-up of phase I KAT301 study Leikas, Aleksi J. Hassinen, Iiro Hedman, Antti Kivelä, Antti Ylä-Herttuala, Seppo Hartikainen, Juha E. K. Gene Ther Article In phase I KAT301 trial, intramyocardial adenovirus-mediated vascular endothelial growth factor -D(ΔNΔC) (AdVEGF-D) gene therapy (GT) resulted in a significant improvement in myocardial perfusion reserve and relieved symptoms in refractory angina patients at 1-year follow-up without major safety concerns. We investigated the long-term safety and efficacy of AdVEGF-D GT. 30 patients (24 in VEGF-D group and 6 blinded, randomized controls) were followed for 8.2 years (range 6.3–10.4 years). Patients were interviewed for the current severity of symptoms (Canadian Cardiovascular Society class, CCS) and perceived benefit from GT. Medical records were reviewed to assess the incidence of major cardiovascular adverse event (MACE) and other predefined safety endpoints. MACE occurred in 15 patients in VEGF-D group and in five patients in control group (21.5 vs. 24.9 per 100 patient-years; hazard ratio 0.97; 95% confidence interval 0.36–2.63; P = 0.95). Mortality and new-onset comorbidity were similar between the groups. Angina symptoms (CCS) were less severe compared to baseline in VEGF-D group (1.9 vs. 2.9; P = 0.006) but not in control group (2.2 vs. 2.6; P = 0.414). Our study indicates that intramyocardial AdVEGF-D GT is safe in the long-term. In addition, the relief of symptoms remained significant during the follow-up. Nature Publishing Group UK 2021-10-01 2022 /pmc/articles/PMC9159942/ /pubmed/34593990 http://dx.doi.org/10.1038/s41434-021-00295-1 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Leikas, Aleksi J.
Hassinen, Iiro
Hedman, Antti
Kivelä, Antti
Ylä-Herttuala, Seppo
Hartikainen, Juha E. K.
Long-term safety and efficacy of intramyocardial adenovirus-mediated VEGF-D(ΔNΔC) gene therapy eight-year follow-up of phase I KAT301 study
title Long-term safety and efficacy of intramyocardial adenovirus-mediated VEGF-D(ΔNΔC) gene therapy eight-year follow-up of phase I KAT301 study
title_full Long-term safety and efficacy of intramyocardial adenovirus-mediated VEGF-D(ΔNΔC) gene therapy eight-year follow-up of phase I KAT301 study
title_fullStr Long-term safety and efficacy of intramyocardial adenovirus-mediated VEGF-D(ΔNΔC) gene therapy eight-year follow-up of phase I KAT301 study
title_full_unstemmed Long-term safety and efficacy of intramyocardial adenovirus-mediated VEGF-D(ΔNΔC) gene therapy eight-year follow-up of phase I KAT301 study
title_short Long-term safety and efficacy of intramyocardial adenovirus-mediated VEGF-D(ΔNΔC) gene therapy eight-year follow-up of phase I KAT301 study
title_sort long-term safety and efficacy of intramyocardial adenovirus-mediated vegf-d(δnδc) gene therapy eight-year follow-up of phase i kat301 study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9159942/
https://www.ncbi.nlm.nih.gov/pubmed/34593990
http://dx.doi.org/10.1038/s41434-021-00295-1
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