Date: 2015-01-27
Type of information: Presentation of results at a congress
phase: 3
Announcement: presentation of results at the 2015 Phacilitate Annual Cell & Gene Therapy Forum in Washington
Company: Taxus Cardium (USA - CA)
Product: Generx® (alferminogene tadenovec [Ad5FGF-4])
Action
mechanism: gene therapy. Generx [Ad5FGF-4] is an angiogenic gene therapy product candidate. It includes a myocardial delivery vector; a therapeutic transgene and proprietary methods of gene therapy. The construct utilizes an adenovirus serotype 5 delivery vector that is replication-deficient, non-integrating and drives short-term transient expression of the Fibroblast Growth Factor-4 (FGF-4) transgene. The product is designed to stimulate the body's natural healing response to ischemic coronary artery disease by promoting microvascular angiogenesis and arteriogenesis, and enhancing cardiac perfusion. When administered by an interventional cardiologist into the coronary arteries under transient ischemic conditions through the use of a standard balloon catheter, Generx distributes into the heart's microvascular pathways and transfects heart cells by binding to cell surface coxsackievirus-adenovirus receptors. These receptors are found throughout the heart, and the binding of Generx to these receptors is enhanced by the induction of transient ischemia and the use of agents like nitroglycerin to boost cell permeability during administration.
The transfected heart cells then express and release FGF-4 protein, which promotes the growth of new blood vessels that increase blood flow to ischemic heart tissue. In addition, the Generx FGF-4 transgene has been modified to include a signal peptide, which allows its effective secretion from cells that express the protein (such as cardiac myocytes). Preclinical studies showed that therapeutic efficacy is significantly increased by the presence of such a signal sequence in the growth factor DNA construct.
Disease: stable angina pectoris
Therapeutic area: Cardiovascular diseases
Country: Russian Federation
Trial
details: The purpose of this study is to determine whether a single intracoronary infusion of Ad5FGF-4, delivered during induced transient ischemia, is effective in improving myocardial perfusion, angina functional class, patient symptoms, and quality of life. Short-term (8 weeks) and long-term (12 month) safety of Ad5FGF-4 will also be evaluated. The primary endpoint is change in adenosine triphosphate (ATP) stress SPECT reperfusion defect size. (NCT01550614)
Latest
news: * On January 27, 2015, Taxus Cardium Pharmaceuticals Group announced a presentation at the 2015 Phacilitate Annual Cell & Gene Therapy Forum in Washington. The review and clinical update, entitled "Progress in Angiogenic Gene Therapy for Coronary Artery Disease" was presented by the Company's Chief Scientific Officer, Gabor M. Rubanyi, M.D., Ph.D.
Dr. Rubanyi outlined the current scientific knowledge about the mechanistic basis of adaptive coronary collateral growth, the biological processes that are targeted by therapeutic angiogenesis discoveries and teachings based on Company-sponsored pre-clinical and clinical research, and provided an update on the Generx microvascular gene therapy Phase 3 international clinical study. He reported that only about 20%-30% of patients with coronary artery disease have well developed coronary collateral networks, and independent clinical studies have confirmed that well established collateral networks can reduce myocardial ischemia, infarct size following a heart attack, and cardiovascular mortality. Dr. Rubanyi further noted that the Company has identified a range of patients with cardiac conditions and syndromes, experiencing persistent myocardial-driven angina due to cardiac microvascular insufficiency, who may also benefit from the Generx microvascular therapy product candidate, despite the etiology of their disease.
