1. The American College of Cardiology Presented by Dr. Timothy Henry
AGENT-3 Trial
A Multicenter, Prospective, Randomized Trial of Intracoronary Administration of Ad5FGF-4 in Patients With No Revascularization Options (AGENT-3) Trial
Presented at
The American College of Cardiology
Scientific Sessions 2005
Presented by Dr. Timothy Henry

2. AGENT-3 Trial Amino Acid Protein Ad5FGF-4 n=150 Amino Acid Protein
415 patients with CCS Class 2-4 angina despite optimal medical treatment not in need of immediate traditional revascularization strategies, able to walk between 3 & 10 minutes with inducible ST depression of at least 1 mm and variability between successive exercise tests of 20% or less, at least 1 proximal vessel with <70% stenosis
Placebo controlled, randomized, blinded, mean follow-up 5 years (data reported for 1 year)
Amino Acid Protein
Ad5FGF-4
1*1010 virus particles
n=150
Amino Acid Protein
Ad5FGF-4
1*109 virus particles
n=150
Control
n=150
Primary Endpoint: Change in exercise tolerance test (ETT) time from baseline to 12 weeks and the proportion of patients with 30% greater increase in treadmill exercise duration in 12 weeks.
Secondary Endpoint: Time to a number of patients with coronary events (non-fatal MI, unplanned hospitalization or revascularization for myocardial ischemia), death at 12 months, time to ST depression, angina, and quality of life parameters.
Presented at ACC2005

3. AGENT-3 Trial: Primary Endpoint
Primary endpoint of change in ETT duration
The primary endpoint of change in ETT duration at 12 weeks was not significant. There was also no change in exercise duration at 6 months.
In a pre-specified analysis, older patients (>55 years) with more severe angina (CCS Class 3 or 4) had a significantly greater increase in ETT at 12 weeks (p=0.02 high-dose, p=0.08 low-dose) and 6 months (p=0.08 high-dose, p=0.07 low-dose).
Similarly, older patients (>55years) with exercise time 300 seconds or less had a significantly greater increase in ETT time at 12 weeks (p=0.03 high-dose, p=0.06 low-dose) and 6 months (p=0.017 high-dose, p=0.03 low-dose).
Presented at ACC 2005

4. AGENT-3 Trial: Subgroup Analysis
p=NS
The combined endpoint of coronary events or death at 1 year in patients completing 12 month follow-up did not differ significantly among the three groups. %
Presented at ACC 2005

5. AGENT-3 Trial: Summary
This study is the largest randomized gene therapy trial for myocardial angiogenesis.
Ad5FGF-4 was not associated with increased exercise time compared to placebo
The favorable safety profile of this drug seen in this trial makes further evaluation using higher doses possible.
The beneficial effect demonstrated in the pre-specified subgroup analysis of higher risk patients warrants further study.
Presented at ACC 2005