VEGF Gene Therapy for Heart Failure Reaching Phase III Trials

Gene therapy, using Vascular Endothelial Growth Factor 121 (AdVEGF121, Biobypass, GenVec, Gaithersburg, MD), effectively induces regrowth of blood vessels and improves exercise tolerance in patients with end-stage heart disease who are not candidates for surgery, researchers told attendees of the American Heart Association’s Scientific Sessions 2002 on Wednesday.

Dr. Duncan John Stewart, of St. Michael’s Hospital in Toronto, on behalf of the REVASC investigators, presented phase II results of 71 “no-option” patients with endstage heart failure randomized to either maximal medical management or VEGF therapy.

Patients in the active therapy group received as many as 30 injections of VEGF directly into all regions of the left ventricle via a minithoractomy.

At 12 weeks, there was no significant difference between the two groups in terms of exercise tolerance. However, at 26 weeks, there was an increase of more than a minute in exercise tolerance in the VEGF group and a statistically significantly longer time to ST segment change on exercise compared with controls. Time to onset of angina with exercise was more than 3 minutes in the active treatment group, significantly longer than in controls. NYHA class improvement was also noticeable in the VEGF group, while there was none in controls.

Dr. Stewart said that quality of life measures were all better in the VEGF group than controls.

There were 10 cases of major adverse events in the study group compared with 11 in controls. There were 2 deaths in the VEGF group compared with 1 in controls. Dr. Stewart said that both deaths in the study group were related to the minithoracotomy procedure rather than to VEGF therapy itself. There was one case of cancer in the study group, which was a recurrent bladder cancer and unrelated to treatment, Dr. Stewart believes.

The REVASC group is planning phase II studies, but Dr. Stewart told Reuters Health that the team will need to change their method of VEGF delivery to one that is catheter-based, in order to avoid the problems of thoracotomy.

Dr. Stewart said that the endpoints should also not be measured so early. “It takes some time for blood vessels to form,” he said. “But [VEGF therapy] appears to have a durable effect, which appears to be lasting even longer than the follow-up in this study.”