FGF-1 has been studied in two investigator-sponsored human Phase I trials led by Phage’s CMO, Dr. Stegmann. These studies demonstrated the ability of FGF-1 to stimulate the growth of “neo-vessels” and the repair of damaged myocardium. FGF-1 is reported to function by promoting angiogenesis in ischemic/hypoxic tissues following an intramyocardial injection in patients with “end-stage” coronary heart disease.
Despite advances in preventive healthcare, medical management, interventional cardiology and cardiac surgery, coronary artery disease (CAD) continues to be a leading cause of morbidity and mortality in the USA. The number of cardiac interventions continues to increase annually: a total of 1.3 million inpatient cardiac catheterizations, 561,000 percutaneous transluminal coronary angioplasty (PTCA) procedures and 519,000 coronary artery bypass procedures (CABG) were performed in 2008 in the USA alone. In the same year, coronary heart disease was responsible for one out of every five deaths and continues to be the number one killer in the USA. In addition, the total number of inpatient cardiovascular operations and procedures increased 27%, from 5,382,000 in 1997 to 6,846,000 in 2007 (National Heart, Lung, and Blood Institute computation based on National Center for Health Statistics annual data; AHA Update 2011).
Phase I clinical trials
Dr. Stegmann performed two academic clinical studies in subjects with advanced coronary heart disease. In the first clinical study, 40 subjects undergoing bypass surgery were randomized equally between 10 µg/kg of active FGF-1 or the heat-inactivated protein. Evaluation of these subjects at three months post-treatment found no adverse events from the growth factor injection. In subjects receiving FGF-1, there was an approximately three-fold increase in microvascular density in the treated myocardium compared with the control group as determined by angiographic gray scale in the injection region. Localized angiogenesis in the FGF-1-treated myocardium was demonstrated to persist over 3 years.
In a second clinical study, 20 subjects with advanced and/or diffuse coronary heart disease who were ineligible for either bypass surgery or angioplasty were treated. The results of this second clinical trial demonstrated that 80% of subjects showed a significant improvement in their bicycle exercise test, and that perfusion of the heart under stress exhibited a significant 2-fold increase in the stress SPECT perfusion score as judged by two treatment-blinded observers at 12 weeks post-dose.