Refractory Angina Gene Therapy XC001 Sustains Effect at 12 Months

XyloCor Therapeutics’ encoberminogene rezmadenovec (also known as XC001 and AdVEGFXC1), an investigational gene therapy intended to treat refractory angina, has shown a sustained effect on several efficacy measures in patients who reached 12 months of follow-up in the extension period of the phase 1/2 EXACT clinical trial (NCT04125732).¹

The extension evaluated patients who had previously been assessed at the 6-month time point after being treated with XC001. XyloCor reported that at the 12-month time point, sustained and continued increases in total exercise duration over baseline measurements were observed. Furthermore, sustained reductions in episodes of angina and nitroglycerin use were reported in the patient population. A sustained decrease in ischemic burden over time was also noted. Xylocor additionally stated that at the 12-month time point, cardiac imaging provided support for the gene therapy’s effect taking place via its expected mechanism of action. XC001 is intended to reduce ischemic burden by increasing expression of vascular endothelial growth factor to induce the creation of new blood vessels. It is delivered as a 1-time treatment.

“The durability and, in the case of exercise time, continued improvements observed at 12 months signals a sustainable activity which is an exciting step forward in the advancement of gene therapy for cardiovascular disease,” Thomas Povsic, MD, PhD, a professor of medicine at Duke University School of Medicine and the national principal investigator for the EXACT study, said in a statement.¹ “These 12‑month data build upon the positive results achieved at the 3- and 6‑month marks of the trial. In total, the outcomes of the EXACT study form a robust body of mechanistic evidence to propel the next stage of XC001’s development, suggesting that a single treatment may have long‑term benefit.”

Results from the 6-month time point were announced in January of this year.² At that time, decreases in ischemic burden on cardiac positron emission tomography imaging were reported in the patients. It was also noted that nearly half of the participants were able to engage in normal physical activity without angina at 6 months posttreatment, despite the fact that prior to administration of the therapy, almost all of the participants' physical activity was substantially limited. At the time, Xylocor also stated that there were no unexpected serious adverse events (AEs) observed in relation to the therapy’s administration and no safety issues related to the therapy itself.

Earlier safety data from the phase 1 portion of the study were announced in May 2022.³ The first phase treated 12 patients, and among 7 of these participants there were 17 serious AEs reported by 6 months of follow-up, but none were deemed related to XC001. The AEs included 6 events deemed related to the administration procedure for the gene therapy, which is done via a minithoracotomy, and 11 events deemed related to the underlying disease or other causes. Xylocor stated that the 6 administration-related AEs occurred in 4 patients and were not considered to be unexpected.

“With the 12‑month results from our EXACT trial, XyloCor continues to take a lead role in fulfilling the promise of gene therapy for people with cardiovascular disease,” Al Gianchetti, the president and CEO of XyloCor, added to the statement.¹ “These results further enhance our confidence that we are on the right path for transforming outcomes in cardiovascular disease.”

REFERENCES
1.XyloCor Therapeutics reports sustained results in 12-month extension of phase 2 EXACT clinical trial of XC001 novel gene therapy for refractory angina. News release. XyloCor Therapeutics. July 18, 2023. Accessed July 19, 2023. http://www.xylocor.com/pdfs/XyloCor-press-release-EXACT-12-month-results-2023-JUL18.pdf
2. 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 July 19, 2023. http://www.xylocor.com/pdfs/XyloCor-Phase-2-Results-Press-Release-2023.pdf
3. 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 July 19, 2023. http://www.xylocor.com/pdfs/XyloCor-PR-Phase-1-Data-Rls-2022-MAY18.pdf