Update on Cardium Therapeutics' plans for commercial development of Generx

Cardium Therapeutics (NYSE Amex: CXM) reported today that its Cardium Biologics division provided an update on plans for the continuing commercial development of Generx™ (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>

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>

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.

SOURCE Cardium Therapeutics