Cardium reported mixed results from two phase IIb/III trials of Generx (alferminogene tadenovec, Ad5FGF-4) for the treatment of chronic angina. These randomized, double-blind, placebo-controlled trials were dubbed AGENT (Angiogenic GENe Therapy -3 and -4 and enrolled a total of 532 subjects in the US and Europe. Subjects received a low dose or high dose of Generx, administered via intracoronary infusion or placebo for 12 weeks. The primary endpoint was the change from baseline in exercise treadmill time (ETT) at 12 weeks and at secondary time points of 4 weeks and 6 months. Secondary endpoints included time to 1 mm ST-segment depression, time to onset of angina and change in Canadian Cardiovascular Society (CCS) class. Pooled data showed no significant difference in the active groups versus placebo in the primary endpoint.
There was a large and significant placebo effect compared with baseline, which persisted over 6 months. In addition, none of the secondary endpoints were achieved with the exception of change in CSS class; significant improvement over placebo only for the high-dose group was observed at week 12, month 6, and month 12 (p< 0.05).
However, in a pooled analysis of pre-specified subgroups statistically significant results were seen among women in all the primary and secondary endpoints as compared to placebo. These were observed at both the three and six month evaluation endpoints for the high dose group (p less than 0.01 to p less than 0.05). In addition, treatment with the low dose of Generx showed statistically significant results over placebo in ETT at three and six months, time to ST-segment depression at six months, and CCS Class at twelve months (p less than 0.05).
Based on the results, Cardium created an FDA approved adjusted clinical protocol and is currently conducting a phase III study in women with angina.