Gene Therapy for Refractory Angina Promotes Increased Exercise Tolerance

Late-breaking data presented at the 2022 American Society of Gene and Cell Therapy Annual Meeting, taking place May 16-19, 2022 in Washington, DC, demonstrate good safety and promising efficacy for an investigational gene therapy to address refractory angina.

The results, presented by Thomas Povsic, MD, PhD, professor of medicine and cardiology, Duke Clinical Research Institute, point to a clinically meaningful benefit for this patient population which has a high burden of disease.

“We think this has the possibility of greatly impacting their quality of life and decreasing their resource utilization," Povsic, who is primary investigator on the EXACT trial, told CGTLive in an interview.

The phase 1/2 clinical trial (NCT04125732) is examining epicardial administration of encoberminogene rezmadenovec (XC001), a replication-deficient adenoviral serotype 5 vector that expresses multiple isoforms of vascular endothelial growth factor (VEGF) including isoforms -121, -165, and -189. Twelve patients with refractory angina have been enrolled and underwent mini thoracotomy to recieve a one-time administration of the investigational therapy across 4 dose cohorts: 1x10⁹, 1x10¹⁰, 4x10¹⁰, and 1x10¹¹.

Notably, of the 17 serious adverse events recorded, none were related to the study drug. Three treatment-related AEs were reported in the high-dose group and included fever, fatigue, and lip swelling. At month 3 and through month 6, a dose-dependent effect was observed, with recorded improvements in mean total excercise duration of 0.6, 0.5, 1.1, and 2.0 minutes in cohorts 1 through 4, respectively.

"This degree of improvement in exercise tolerance is associated with improvements in mortality," Povsic told CGTLive. "While these patients don’t suffer from a high rate of mortality, it's important to realize this improvement in exercise tolerance is really clinically significant.”

Based on the findings, the phase 2 dose-expansion portion of the study will move forward at the highest dose.

Watch our interview below for more details about the findings.

REFERENCE

Povsic TJ, Traverse JH, Henry TD, et al. Preliminary Safety, Tolerability and Efficacy of Direct Epicardial Administration of Encoberminogene Rezmadenovec to Ischemic Myocardium in Patients with Refractory Angina: Six Month Phase 1 Data. Presented at: 2022 American Society of Gene and Cell Therapy Annual Meeting; May 16-19, 2022; Washington, DC.