Gene therapy helped refractory angina in phase 2 trial

American researchers have reported success in a phase II multicenter open-label, multicenter clinical trial of gene therapy for refractory (drug-naive) angina pectoris. The report was presented at the Scientific Sessions of the Society for Cardiovascular Angiography and Interventions SCAI 2024. In the EXACT trial, Kenta Nakamura of the University of Washington and colleagues administered the experimental drug XC001 (AdVEGFXC1, encoberminogen resmadenovec) to 32 patients with refractory angina pectoris. It represents the gene for vascular endothelial growth factor (VEGF), which stimulates vascular growth (angiogenesis), on an adenovirus-5 vector. It was injected once transepicardially into the myocardium at a dose of 1 × 1011 vector genomes.

No serious drug-related adverse events were reported; in 13 patients, they occurred in association with surgical access to the heart but were managed. The mean duration of tolerated treadmill exercise increased from baseline 359.9 seconds to 448.2 by the third month; 449.2 by the sixth month; and 477.6 by the twelfth month. Total myocardial perfusion deficit as measured by PET/CT decreased by 10.2; 14.3; and 10.2 percent at these time points, respectively. The time to ST-segment depression on the ECG during exercise (an indicator of myocardial ischemia) increased by 105.2; 113.6 and 103.1 seconds; the frequency of angina attacks decreased by 7.7; 6.6 and 8.8 episodes. Functional class of angina improved in 81 percent of patients. Administration of XC001 was recognized as safe and generally well tolerated; a persistent effect over a year was considered to warrant continuation of the trial.