Groundbreaking angiogenic gene therapy shows promise in refractory angina: EXACT Phase 2 trial

According to the trial, gene therapy for therapeutic angiogenesis showed promise for patients with angina who had already exhausted their options for medical therapy and coronary revascularization. The findings were published online in Circulation: Cardiovascular Interventions.

"XC001, an engineered adenovirus vector that transiently increases VEGF-A expression in the myocardium, administered via transepicardial delivery is safe and generally well tolerated," the researchers reported. "Exploratory improvements in ischemic burden, total exercise duration, and subjective measures support a biological effect sustained to 12 months, warranting further investigation."

XC001 is a novel adenoviral-5 vector designed to express multiple VEGF (vascular endothelial growth factor) isoforms and more safely and potently induce angiogenesis. Kenta Nakamura, Division of Cardiology, Department of Medicine, University of Washington, Seattle. (K.N.), and colleagues conducted the EXACT trial to assess the safety and preliminary efficacy of XC001 in patients with no option refractory angina.

The single-arm, multicenter, open-label trial included 32 patients with no option refractory angina who received a single treatment of XC001 (1×1011 viral particles) via transepicardial delivery.

The researchers reported the following findings:

• 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 of 359.9 seconds at baseline to 448 (3 months), 449.2 (6 months), and 477.6 (12 months; +88.3, +84.5, and +115.5).
• Total myocardial perfusion deficit on positron emission tomography imaging decreased by 10.2%, 14.3%, and 10.2%.
• Angina frequency decreased from a mean of 12.2 episodes to 5.2 (3 months), 5.1 (6 months), and 2.7 (12 months), with an average decrease of 7.7, 6.6, and 8.8 episodes at 3, 6, and 12 months.
• Angina's class improved in 81% of participants at six months.

While further research is warranted to validate these findings and optimize treatment protocols, the results of the EXACT Phase 2 Trial signify a paradigm shift in the approach to refractory angina management. With continued advancements in gene therapy technology, the prospect of personalized, targeted treatments for ischemic heart disease looms on the horizon, promising renewed hope for patients facing this challenging condition.

Reference:

Nakamura K, Henry TD, Traverse JH, Latter DA, Mokadam NA, Answini GA, Williams AR, Sun BC, Burke CR, Bakaeen FG, DiCarli MF, Chaitman BR, Peterson MW, Byrnes DG, Ohman EM, Pepine CJ, Crystal RG, Rosengart TK, Kowalewski E, Koch GG, Dittrich HC, Povsic TJ; EXACT Trial Investigators. Angiogenic Gene Therapy for Refractory Angina: Results of the EXACT Phase 2 Trial. Circ Cardiovasc Interv. 2024 May 2:e014054. doi: 10.1161/CIRCINTERVENTIONS.124.014054. Epub ahead of print. PMID: 38696284.