Refractory Angina Gene Therapy Demonstrates Safety and Efficacy in Phase 2 Trial


Nearly half of participants were able to engage in normal physical activity without angina at 6 months post-treatment.

XyloCor Therapeutics’ XC001 (AdVEGFXC1), an investigational gene therapy intended to treat refractory angina, has demonstrated promising safety and efficacy in newly announced data from the phase 2 portion of the phase 1/2 EXACT clinical trial (NCT04125732).1

XC001 is delivered locally to the heart muscle via a transthoracic epicardial procedure as a 1-time treatment. It is intended to increase the expression of vascular endothelial growth factor (VEGF) in order to induce the creation of new blood vessels, which is expected to reduce ischemic burden. The phase 2 portion of EXACT treated 28 patients. At 6 months of follow-up, decreases in ischemic burden on cardiac positron emission tomography (PET) imaging were observed in the patients. It was additionally noted that prior to administration of the therapy, almost all of the participants' physical activity was substantially limited, while nearly half of the participants were able to engage in normal physical activity without angina at 6 months post-treatment. In terms of safety, there were no unexpected serious adverse events (AEs) observed in relation to the therapy’s administration, and no safety issues related to the therapy were reported.

"We are excited to see EXACT completing its 6-month endpoint,” Thomas Povsic, MD, PhD, professor of Medicine, Duke University School of Medicine, and national principal investigator for the EXACT study, said in a statement regarding the news.1 “The trial met all of its safety and exploratory objectives, showing intriguing benefits in these needy patients across a variety of objective and subjective measures. The strong range of mechanistic evidence demonstrate that administration of XC001 is a scientifically-sound approach for achieving a biological effect that has the potential to improve patients’ quality of life."

The phase 2 data builds on the results of the trial’s phase 1 portion, data from which were announced in May 2022.2 Among 7 of the 12 patients treated in the first phase, there were 17 serious AEs reported by 6 months of follow-up, but none were deemed related to the gene therapy. These AEs included 6 events deemed related to the administration procedure for XC001 and 11 events deemed related to the underlying disease or other causes. The 6 administration-related AEs occurred in 4 patients and were not considered to be unexpected.

The multicenter, open-label EXACT study enrolled 41 participants in total, with an age eligibility of 18 years to 80 years. The phase 1, dose-escalation portion treated participants at 4 ascending dose levels, with 3 participants in each dose cohort: 1x109 vp, 1x1010 vp, 4x1010 vp, and 1x1011 vp. A dose-dependent correlation was inferred based on a preliminary efficacy data analysis, and as such, the highest of the dose levels was selected for the study’s phase 2 expansion portion. The trial’s primary end point is safety as assessed by AEs and serious AEs. Secondary end points include an exercise tolerance test, the Seattle Angina Questionnaire, Canadian Cardiovascular Society angina class, and angina episodes.

"We are excited to share this positive topline data from the phase 2 portion of the EXACT trial, reinforcing our confidence in XC001 as a novel therapeutic approach with the potential to address the significant unmet medical needs of people with refractory angina," Al Gianchetti, president and chief executive officer, XyloCor Therapeutics, added to the statement.1 "We now look forward to pursuing key upcoming milestones in XC001’s continued development, including finalizing our pivotal trial design through our ongoing discussions with the FDA and other regulatory authorities."

1. Xylocor Therapeutics reports positive topline safety and efficacy results from phase 2 EXACT clinical trial of XC001 novel gene therapy for refractory angina. News release. XyloCor Therapeutics. January 26, 2023. Accessed January 26, 2023. 
2. Xylocor Therapeutics announces presentation of preliminary clinical data from phase 1 portion of the EXACT phase 1/2 study of XC001 novel gene therapy for refractory angina at AATS and ASGCT. News release. XyloCor Therapeutics. May 18, 2022. Accessed January 26, 2023. 
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