GenVec Inc announced Phase II clinical data for its lead cardiovascular product candidate, Biobypass angiogen, in patients with severe coronary artery disease. The Phase II Biobypass clinical trial, called the REVASC trial, involved 20 sites in North America and 71 patients with severe coronary artery disease were enrolled. It is the largest, randomized, controlled study reported to date with intramyocardial injection of genes coding for angiogenic growth factor.

The REVASC study was designed to explore the safety and efficacy of Biobypass in patients with severe coronary artery disease. Biobypass is designed to improve blood flow to the ischemic areas of the heart. Biobypass induces new blood vessel growth, a process known as angiogenesis, which may improve heart function and patient well-being.

Biobypass works by providing local delivery of the gene encoding for Vascular Endothelial Growth Factor, or VEGF, the human body's natural stimulator of new blood vessel growth. Biobypass is delivered to the heart by a method known as intramyocardial injection.

The study was designed to capture a wide-range of endpoints to assess the treatment effect of Biobypass on patients with severe coronary artery disease. Patients were randomized into two groups where 36 patients were treated with Biobypass therapy plus best medical treatment and 35 patients received best medical treatment only and served, for purposes of comparison, as a control group.

The primary analysis was selected to objectively measure the impact of the Biobypass treatment. This end point quantifies ischemia in the heart by measuring a specific change on the Electrocardiogram, known as ST segment depression. A physician who had no knowledge of what treatment the patient received assessed this endpoint in a blinded fashion at a central core laboratory.

A number of secondary end points were included to assess the impact of Biobypass on patient's symptoms and functions. Measures included time to chest pain on a treadmill, total exercise time, patient quality of life assessment (Seattle Angina Questionnaire), as well as a health care professional's assessment of patient function (Canadian Cardiovascular Society Angina Class).

All parameters were analyzed at baseline and three and six months after treatment to assess the durability of the effects.

Patients in the REVASC study had severe, advanced coronary artery disease. The patients generally suffered from severe chest pain known as angina, despite receiving maximal medical treatment. The majority of the patients in the REVASC study had already received standard revascularization procedures such as angioplasty and coronary artery bypass grafts, and were not candidates for any other surgical intervention.

The primary analysis showed a trend towards improvement in the Biobypass group in ST segment depression at 3 months (primary endpoint) of 24 seconds (p=0.35) which improved to 1.1 minutes (28% increase over baseline) at 6 months which was a statistically significant difference from the control group (p=0.024).

There were significant improvements in total time to chest pain on the treadmill and total exercise time on the treadmill at both 3 and 6 months. For example, at 6 months post treatment, the time to angina increased by 1.5 minutes from baseline, corresponding to a 37% increase in the Biobypass group as compared to the control group, which was unchanged (p=0.002). These endpoints are widely accepted as a measure of patient benefit.

Significant improvements in patient quality of life were seen at 6, 12 and 26 weeks as assessed by the Seattle Angina Questionnaire. Measures of these improvements included the patient's ability to get dressed, to resume play with their children or grandchildren, and a reduced need for cardiovascular medications. The magnitude of improvement seen was similar to what has been observed after angioplasty.

Significant improvements in patient function were also assessed by healthcare professionals through the Canadian Cardiovascular Society Angina Class Questionnaire. Again, significant improvements were seen at 6, 12 and 26 weeks.

Continuous improvements from 3 to 6 months were consistently seen across all of these endpoints. Biobypass was well tolerated and there was no difference in serious adverse events noted between the Biobypass group and the control group.

Dr. Duncan Stewart, Chief of Cardiology and Internal Medicine at St. Michael's Hospital in Toronto and principal investigator for the Biobypass clinical trial commented, "This study provides the first clear-cut 'proof-of- concept' that angiogenic gene therapy with Vascular Endothelial Growth Factor works in patients who have advanced coronary artery disease, severe angina pectoris and no other options for revascularization." Dr. Stewart continued, "I am particularly pleased with the significant improvement in all exercise parameters after 26 weeks, which indicates that the effect is durable. This is a milestone in the evolution of cardiovascular gene therapy, and could, if confirmed in larger studies, provide a new treatment paradigm for patients with advanced coronary artery disease."

Henrik Rasmussen, Senior Vice President for Clinical Research and Regulatory Affairs at GenVec, stated, "We are very pleased with the data presented, demonstrating that Biobypass is associated with substantial functional as well as symptomatic benefit in patients with severe coronary artery disease. Since GenVec has already demonstrated the feasibility of delivering Biobypass with a catheter in a Phase I study, the next step for GenVec in the development of Biobypass for coronary artery disease will be a large, randomized, placebo-controlled, pivotal study using catheter-based drug delivery in the same patient population."

Injection of Biobypass delivers the Vascular Endothelial Growth Factor, or VEGF, gene directly to areas of the heart with poor blood flow. Based upon preclinical mechanism of action studies, the gene stimulates localized production of the VEGF protein to promote angiogenesis, or growth of new blood vessels, and to improve blood circulation.