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Home > Press Center > Press Releases from 2005 Annual Meeting > Gene therapy does not prevent leg vein graft failure study

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Jill Goodwin
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A form of gene therapy used on vein grafts before implanting them into patients’ lower legs failed to keep the grafts from narrowing down or needing revision within a year, according to a study presented at the annual meeting of the Society for Vascular Surgery. Researchers had hoped that the gene therapy on the grafts would work because the 5-year failure rate of standard vein grafting is 40 percent, and no postoperative medication has been effective at preventing graft failure.

The study (co-sponsored by Corgentech, Inc. and Bristol Myers Squibb) was conducted at 83 sites throughout North America and involved 1,404 patients who had critical limb ischemia (CLI), in which circulation to the lower legs and feet is impaired by blockage of the vital arteries there. The graft surgery involves “harvesting” vein segments from the patient and implanting them to act as “replacement” arteries, to improve circulation. In this study, the vein grafts from 707 patients were treated with the investigational drug edifoligide after being harvested but before implantation, while the grafts from the remaining 697 patients underwent a sham treatment with a placebo substance. Edifoligide is a small molecule composed of the same chemical material (DNA) that makes up our genes, but only 1/1000th the size of an actual gene. The drug was designed to block the growth of cells in the vein, which is felt to be responsible for the narrowing that occurs in some patients after bypass surgery. In previous studies, edifoligide had been found to prevent the overgrowth of the cells lining the blood vessels and to prevent the buildup of atherosclerotic plaque there. The researchers hoped that these properties would prevent the grafts from narrowing over time. They also believed that leg vein grafting was particularly well-suited to a genetic therapy because the treatment could be applied outside of the patient’s body, where it would affect only the vein graft and not any other tissues, said Dr. Michael S. Conte of Brigham and Women’s Hospital, Boston.

However, one year later there were no differences between the two groups of patients in the rates of graft narrowing, further interventions to treat impaired circulation, limb salvage, or patient survival. “Edifoligide did not confer protection from graft failure,” he said. Despite a negative result on the primary trial endpoints, the investigators found that secondary patency of the grafts, a measure which includes the ability to preserve grafts with repeat invasive  procedures, was improved by edifoligide, suggesting some element of biological effect which may need further study.

CLI is an advanced form of the peripheral artery disease that affects 20 percent of Americans aged 70 and older. In CLI the arteries to the legs and feet are blocked, cutting off vital circulation there. This can cause ulcerations that won’t heal, infections, and even gangrene of the toes, feet, and lower legs, which can lead to amputation. In most cases the arteries are blocked by atherosclerosis, or plaque buildup within the arteries. CLI usually is associated with high blood pressure, diabetes, heart disease, or stroke.