SAN DIEGO, Jan. 26 Cardium Therapeutics (NYSE Amex: CXM) reported today that its Cardium Biologics division provided an update on plans for the continuing commercial development of Generx(TM) (alferminogene tadenovec, Ad5FGF-4), a DNA-based angiogenic therapy product candidate for patients with coronary artery disease. The update was presented by Gabor M. Rubanyi, M.D., Ph.D., Cardium's Chief Scientific Officer at the annual 2010 Cell & Gene Therapy Forum in Washington, D.C. on January 25, 2010. An investor presentation that includes material from Dr. Rubanyi's presentation is now available on Cardium's website at http://phx.corporate-ir.net/phoenix.zhtml?c=77949&p=irol-presentations.
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
Reported in Journal of American College of Cardiology
Positive results supporting the proposed mechanism of action of Generx in improving blood flow within ischemic heart tissue were published in JACC, A Randomized, Double-Blind, Placebo-Controlled Trial of Ad5FGF-4 Gene Therapy and its Effect on Myocardial Perfusion in Patients with Stable Angina (Grines et al., J Am Coll Cardiol 2003; 42:1339-47). The results of the study showed improvements in myocardial perfusion (blood flow) in the ischemic region of the hearts of both men and women following a single intracoronary infusion of Generx. Increases in blood flow within the ischemic regions of the heart under the conditions studied (i.e., adenosine infusion) are believed to be due to the formation of new collateral blood vessels capable of providing additional blood flow capacity under stress. Generx was well tolerated in the study of 52 patients (88% men and 22% women) with reversible ischemia of >9%, with no adverse sequelae. As noted in the publication, the mean change observed in Generx-treated patients was a 4.2% absolute reduction (which represents a 20% relative reduction) in the reversible perfusion defect size from baseline at eight weeks (p<0.001), while the placebo group showed only a 1.6% absolute reduction from baseline (not significant). The observed treatment effect for patients receiving Generx was similar in magnitude to that reported in the literature for patients undergoing revascularization procedures (CABG surgery or angioplasty) with reversible perfusion defects of comparable size at one year following these procedures.
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
A long-term study published in the American Heart Association's Journal, Circulation (Meier et al, Circ. 2007; 116:975-983) provided key evidence indicating that men and women with more recruitable collateral circulation have a better chance of surviving a heart attack than patients who have less developed collateral circulation. This important study quantitatively evaluated coronary collateral blood flow in 845 patients with coronary artery disease during a 10-year follow-up period and demonstrated that long-term cardiac mortality was reduced by 75% in patients with a highly developed collateral vessel blood supply (p=0.0395). This study provides new evidence suggesting that patients with more coronary collateral vessel growth have a better chance of surviving a heart attack than patients who have less developed collateral vessel growth.
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
The Generx(TM) (alferminogene tadenovec, Ad5FGF-4) product candidate represents a new class of cardiovascular biologics that is being developed to leverage the body's natural healing processes in response to repeated ischemic stress (insufficient blood flow and myocardial oxygen supply due to coronary heart disease). The natural biologic response to repeated transient ischemia is angiogenesis, the growth of new collateral blood vessels, which is orchestrated by a complex and incompletely understood cascade involving many growth factors. These newly-formed vessels can effectively augment blood flow and oxygen delivery to areas of the patient's heart downstream from a blockage in a coronary artery. In many patients however, including those with recurrent angina, coronary collateral vessel formation is insufficient to meet the heart's needs during stress. Currently available anti-anginal drugs, which may provide symptomatic relief, are generally designed to alter the oxygen demand of the heart muscle or dilate vessels to temporarily relieve angina. Generx is an angiogenic therapeutic that is designed to promote the heart's natural response of collateral growth and to increase blood flow in the microcirculation. In contrast to the transient symptomatic relief provided by marketed anti-anginal medicines, usually taken several times a day for years, a single administration of Generx aims at modifying the disease by permanent or long-lasting structural changes in the heart.
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 as ischemia) 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.
Cardium is focused on the acquisition and strategic development of new and innovative bio-medical product opportunities and businesses that have the potential to address significant unmet medical needs and definable pathways to commercialization, partnering and other economic monetizations. Cardium's investment portfolio includes the Tissue Repair Company and Cardium Biologics, medical technology companies primarily focused on the development of innovative therapeutic products for wound healing, bone repair, and cardiovascular indications. In July 2009, Cardium completed the sale of its InnerCool Therapies medical device business to Royal Philips Electronics, the first asset monetization from the Company's biomedical investment portfolio. News from Cardium is located at www.cardiumthx.com.
Except for statements of historical fact, the matters discussed in this press release are forward looking and reflect numerous assumptions and involve a variety of risks and uncertainties, many of which are beyond our control and may cause actual results to differ materially from stated expectations. For example, there can be no assurance, that results or trends observed in one clinical study or procedure will be reproduced in subsequent studies or procedures, or that clinical studies even if successful will lead to product advancement or partnering; that improvements in the formulation or use of Generx will be commercially practicable, or that Generx could be successfully advanced as a therapeutic in developing markets or that the results of studies in such markets could be used to advance the commercialization of Generx in the U.S. or other markets; that our products or product candidates will not be unfavorably compared to competitive products that may be regarded as safer, more effective, easier to use or less expensive; that FDA or other regulatory clearances or other certifications, or other commercialization efforts will be successful or will effectively enhance our businesses or their market value; that our products or product candidates will prove to be sufficiently safe and effective after introduction into a broader patient population; or that third parties on whom we depend will perform as anticipated.
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.
SOURCE Cardium Therapeutics