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Cardium Biologics reported on the following findings and plans: (1) As previously announced, based on an agreement with the FDA, Generx would be re-formulated to increase its shelf life, and further formulation enhancements are expected to allow for storage using a standard freezer (rather than at -70 degrees C), and potentially a lyophilized version for refrigerated storage. (2) Based on clinical and pre-clinical findings, angiogenic therapy appears to lead to long-term functional improvements in cardiac microvascular circulation, and Cardium believes that cardiac perfusion (as measured by SPECT) appears to be an important efficacy endpoint to consider that is now supported by a 10-year study of the cardio-protective nature of collateral circulation (Meier et al. Circulation 2007; 116:975-83). (3) Recent preclinical data developed by the Company under an SBIR grant indicate that localized ischemia can significantly increase Ad5 transfection in the heart in association with intracoronary infusion therapy, suggesting that cardiac stimulation (using e.g. dobutamine which is routinely administered to patients) in association with administration of Generx has the potential to dramatically enhance the therapeutic effect at a given dose. (4) In order to incorporate these enhanced formulations and perspectives and also expand the clinical database supporting the potential commercialization of Generx, the Company is considering clinical and commercialization pathways for Generx in developing nations that often have very limited access to surgical approaches such as angioplasty, stenting or coronary artery bypass (which are available to patients in industrialized nations but at costs reaching $80,000 to $100,000 per procedure over a five year period). The U.S. and European clinical studies of Generx have collectively established an extensive database supporting the safety of this product candidate, even in patients with severe forms of chronic coronary artery disease. Successful application of this therapy as "front-line care" would be expected to lead to commercialization pathways in many developing markets for which surgical and other relatively expensive approaches are either unavailable or limited by already over-burdened health care systems. In addition, information gained with these new applications would be expected to be useful to support broadened commercialization pathways in the U.S. and other developed markets. "There has been significant progress in the care and treatment of patients with cardiovascular disease in the industrialized world, although at considerable and increasing expense. While heart disease remains a very serious problem in the U.S. and Europe, incidence is rapidly increasing in large parts of the newly-industrializing world such as China, India and Russia, as well as in the Middle East and Latin America. In many countries, healthcare systems are unable to provide wide access to relatively expensive procedures such as coronary angioplasty, stenting, or cardiac bypass surgery. Based on data indicating that the Generx product candidate appears to safe and has the potential to substantially increase coronary blood flow in the context of heart disease - coupled with recent findings that improvements in collateral circulation are associated with long-term benefits, including reduced mortality as reported in a 10-year study published in Circulation - we believe that this product candidate could be developed as a front-line therapy for coronary artery disease. Additional data gained in parallel studies, which would be expected to be conducted in collaboration with specific regional development partners, would also be expected to support an expanded U.S. registration dossier by providing additional safety data and potentially alternative efficacy measures," stated Christopher J. Reinhard, Cardium Chairman and Chief Executive Officer. Mechanism of Action Study: Generx Improves
Blood Flow via Increased Collateral Circulation in Ischemic
Heart Tissue (as
reported in Journal of
American College of Cardiology) Long-term Independent Study Demonstrates that Collateral Circulation
has an Important Protective Role in Chronic Angina Patients and Reduces
Cardiovascular and All-Cause Mortality (as reported in American Heart Association
Journal Circulation) It is well known that transient myocardial ischemia in certain patients with coronary artery disease will stimulate the growth of collateral vasculature and that the extent of pre-existing collateral circulation in patients appears to influence survival after a heart attack by providing alternate routes for myocardial blood flow. While not well understood, patients' inherent capacity to grow this micro-vasculature may be limited due to factors such as the course and progression of their coronary artery disease and their genetic predisposition. This study provides quantitative evidence suggesting that collateral blood flow may improve the prognosis of patients undergoing angioplasty or bypass surgery. Detectable collateral vessel function following angioplasty has been reported, even in patients without evidence of ischemia. Generx Product Candidate Researchers believe that central to the biological activity of Generx is the effective capture of the Ad5 delivery vector in the coronary micro-vascular circulation, subsequent vector uptake, and FGF-4 protein expression in the heart (preferentially myocytes and endothelial cells). The new preclinical studies show that ischemia is a prerequisite for efficient delivery and transfection of Ad5FGF-4 in the heart. The formation of new blood vessels (angiogenesis) and remodeling of existing collateral vessels are the two main mechanisms contributing to the therapeutic effect of an angiogenic growth factor. New micro-vascular circulation development naturally occurs in the embryo, but in the adult organism it requires tissue injury (such asischemia) to initiate a regenerative process, including collateral vessel formation. Research shows that FGF-4 is an important regulatory protein in the pathway that orchestrates the growth of new micro-vascular vessels and their enlargement in the heart. After the FGF-4 protein is secreted or transported out of the myocyte, it acts via high affinity FGF receptors on neighboring endothelial cells to signal the initiation of cardiac angiogenic activity and enhancement of the collateral vessel formation process. These actions of FGF-4 require an ischemic/hypoxic milieu to proceed efficiently. FGF-stimulation may promote the formation of more mature vessels with improved stability, which, combined with appropriate blood flow through them, should contribute to the long term persistence of newly formed collateral vessels. Once the beneficial blood vessel growth or vascular remodeling has been accomplished, and provided there is sustained blood flow through the newly-formed vessels, continued FGF-4 growth factor secretion is no longer needed. Indeed, preclinical studies demonstrated that a single intracoronary infusion of Generx was capable of stimulating new vessel formation in the heart that was associated with improved blood flow and ventricular contractile function, an effect which lasted for at least 3 months. About Cardium Forward-Looking Statements Actual results may also differ substantially from those described in or contemplated by this press release due to risks and uncertainties that exist in our operations and business environment, including, without limitation, risks and uncertainties that are inherent in the development of complex biologics and in the conduct of human clinical trials, including the timing, costs and outcomes of such trials, our ability to obtain necessary funding, regulatory approvals and expected qualifications, our dependence upon proprietary technology, our history of operating losses and accumulated deficits, our reliance on collaborative relationships and critical personnel, and current and future competition, as well as other risks described from time to time in filings we make with the Securities and Exchange Commission. We undertake no obligation to release publicly the results of any revisions to these forward-looking statements to reflect events or circumstances arising after the date hereof. Cardium Therapeutics™ and Generx® and MedPodium™ are
trademarks of Cardium Therapeutics, Inc. Source: Cardium Therapeutics, Inc. |
