Alferminogene tadenovec, an angiogenic FGF4 gene therapy for coronary artery disease

Alferminogene tadenovec is a replication-deficient human adenovirus serotype 5 that encodes human FGF4, an angiogenic protein that enhances the formation of new blood vessels. Following early clinical development by Collateral Therapeutics Inc (now Bayer Schering Pharma AG), Cardium Therapeutics Inc is currently developing alferminogene tadenovec as a potential gene therapy to improve the reperfusion of ischemic myocardium. In phase I and II clinical trials, the administration of alferminogene tadenovec was well tolerated and resulted in significant improvements in treadmill exercise capacity. However, two phase IIb/III clinical trials for the gene therapy were discontinued before completion because a high placebo response had occurred, and the trial was considered unlikely to demonstrate a benefit under the design employed. A post-hoc subgroup analysis revealed a substantial benefit from the therapy in female patients only. A phase III clinical trial is currently evaluating alferminogene tadenovec as a therapy for myocardial ischemia in women who are not candidates for revascularization. If further investigations confirm the safety and efficacy of the gene therapy, then alferminogene tadenovec may be considered a realistic therapeutic option for myocardial ischemia in selected patient populations.