Cardium Therapeutics (AMEX:CXM) announced that buoyant findings from pooled by-patient analysis of the AGENT-3 and AGENT-4 Phase 2b/3 clinical trial will be published contained by means of the September 11, 2007 circulate of the Journal of the American College of Cardiology (JACC) and be in a minute unclaimed online. Among the findings tittle-tattle, a pre-specified analysis showing momentous improvements in multiple clinical measures of heart bug among women who received Generx(TM) (alferminogene tadenovec, Ad5FGF-4) in manufacturing works of compare to women in the placebo cranny the bazaar kind. Generx is mortal amount produced as a impending nurture in favour of man and women near myocardial ischemia (insufficient blood spill inwardly the heart muscle) and associated angina in the red to coronary heart disease and imply a up-to-the-minute liberating colloquium of cardiovascular biologics. Generx is designed to impel angiogenesis, a unprocessed control of vein bung up within the heart muscle, subsequent a one-time intracoronary infusion from a rife cardiac infusion catheter. The Company just now announced that the FDA personal granted Fast Track designation to Generx.
"The AGENT clinical chamber have ensnared beyond 650 patients with heart disease in four double-blinded, placebo-controlled clinical studies at completed 100 medical centers in the U.S. and collective. This represents the maximum advanced clinical program to progress a new non-surgical alternative for the potential disease-modifying treatment of millions of patients interrupt from permanent angina," stated Christopher J. Reinhard, Chairman and CEO of Cardium. "The Generx produce challenger is now the original and simply angiogenic DNA-based line in Phase 3 clinical respect designed to hearten this huge and speedily escalating medical emergency. As a repercussion of these rugged employment, we now have (1) the largest sanctuary database for a cardiovascular DNA-based therapeutic; (2) a appliance of instability study guarantee angiogenic comeback, as measured by myocardial perfusion, in men and women; (3) substantiation portentous a dose response; (4) a measurable and resilient treatment effect; and (5) a concordance of positive grades across multiple gaudy measures of treatment effects in women with coronary heart disease. These findings spoon out as the reason for Cardium's demonstrated Phase 3 AWARE clinical study, which is now in overflowing vacillate and is anticipated to enroll 300 women at up and something approaching to 50 U.S. medical centers. With the realization of the AWARE study, nearly 1,000 patients will have participate in Generx clinical studies involving in the region of 60 percent men and 40 percent women." Findings of the AGENT Studies The most recent article linked to the AGENT studies, relevant "Effects of Ad5FGF-4 in Patients with Angina: An Analysis of Pooled Data from the AGENT-3 and AGENT-4 Trials", will be published in the September 11, 2007 issue of the Journal of the American College of Cardiology (JACC) and is now available online at JACC and by the Company's website here. The pooled analysis previously owned clever forgiving figures compile from two coincident and nearly indistinguishable double-blind, placebo-controlled clinical studies that randomized angina patients to any placebo, in terse endow with dose or high-ranking dose of Generx. These two large-scale trials enrol 532 patients at approximately 100 medical centers for the duration of the United States (AGENT-3) and internationally (AGENT-4).
The current JACC publication, which describe an analysis of pooled pre-specified subgroups, reported statistically significant positive treatment effects in for a while contradictory measures of heart disease among women in the AGENT-3 and AGENT-4 studies (n76). Concordance of multiple significant improvements be observed with the high dose of Generx, effects that be maintain even six months after the one-time intracoronary infusion. These positive findings built-in: (1) an escalate in overall defence in barb on the games treadmill exam or ETT, which is a weigh up of exercise dimensions; (2) an increase in exercise time to 1 mm ST-segment recline on electrocardiogram or ECG, which is related to declining of underlying myocardial ischemia; and (3) a diminution in staunchness of angina (Canadian Cardiovascular Society or CCS Class). Each of these positive effects was statistically significant as compared to placebo at both the three and six month evaluation endpoints for the high dose group (all of which exhibit occasion or "p values" range from p less significant horizontal than 0.01 to p less than 0.05). There were also statistically significant improvements (p less than 0.05) in whichever of these measures within the low dose group, plus ETT at three and six months, time to ST-segment depression at six months, and CCS Class at twelve months. Even after apply idealistic statistical cost adjustment for subgroup analyses, the effects on the primary endpoint in women remain statistically significant (p less than 0.017) for the high dose group, and the statistically significant incongruity relating patients reception Generx versus placebo was perpetual at six months.
The immovability of positive effects was further evidence by the significant advancement observed in women at one year following command with deference to CCS angina class (the efficacy endpoint follow up for an stretched period), a difference that was significant for both the high dose group (p less than 0.017) and the low dose group (p less than 0.05). Additional positive findings come from observations of long-term safety data. In unique, the studies showed that over several years of patient firmness for safety, in the neighbourhood was a statistically significant humiliate rate of recurrence of wear and tear angina among all patients (including both men and women) that had received Generx as compared to patients that had received placebo (p0.04).
In the JACC article, the poet concluded that, "Treatment of women with angina offering a stimulating puzzle considering the underutilization of rearrangement dream therapy and the nearly twin standardized mortality ratio in women compared to men. Management of angina in these patients represents an unmet clinical necessitate specifically more and more becoming one of the most pressing issues in healthcare, mega among the aging population. The potential stress of a gender-specific angiogenic response on the clinical treatment of CAD (coronary artery disease) is great and deserve further oral exam in amply powered clinical trials." Among other findings of the AGENT studies, a high placebo response was observed among in economically brought-up robustness patients with respect to exercise treadmill trialling, an effect that may be accentuate by accompanying exercise or lifestyle change. The fact of such a placebo response, particularly one affecting exercise capacity, tend to watch or blanket potential linctus effects among more exercise-competent subgroups when using test such as the exercise treadmill. In sleeve with those observations, subsidiary analyses of the AGENT-3 and AGENT-4 studies showed that among a subgroup of patients, particularly men who were younger and more rationalized of exercise, there was a substantial placebo response observed on ETT. Among women, who have across the world be under-represented in cardiovascular clinical trials in spite of a high incidence of heart disease, the observed placebo response was substantially less and the observed treatment effect was correspondingly greater. Among all patients (including both men and women) over the age of 55, when patients were more exercise-limited to switch on with, the placebo response was relatively fixed. Importantly, the group of exercise-limited patients that had received Generx sophisticated a substantial improvement in exercise time on ETT whereas the placebo group do not, a difference that was both statistically significant and maintained over time. In the AGENT trials, the women tend to have more chewy angina (as evidenced by CCS class) and were also on vitally more medication, both suggestive of a more severe disease which may have limited the degree of exercise homework.
These and other findings position the U.S. Food and Drug Administration (FDA) to agree to the operate of refurbishment from baseline in exercise time to 1 mm ST-segment depression on ECG as the primary endpoint for Cardium's Phase 3 AWARE study. Time to ST-segment depression is a more forward measure of underlying myocardial ischemia and is believed to be considerably less field to a placebo response. As reported in the recent JACC publication, among women who had received the high dose of Generx in the AGENT-3 and AGENT-4 studies, the improvement in time to ST-segment depression was both statistically significant (p less than 0.017) and sustained for at lowest reasonable 6 months following one-time administration. The secondary endpoints of the Phase 3 AWARE study embrace an additional ambition measure of correct myocardial blood flow within the studied heart muscle, namely adenosine SPECT imaging (single photon breakers count tomography), which was the subject of the AGENT-2 study reported down, above and beyond as improvements in other measures of angina.
In 2003, positive results from the AGENT-2 clinical study 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 - /flash/pdf/JACC_AGENT2.pdf). AGENT-2 was a mechanism of action study designed to measure able to the potential for Generx to incite a therapeutic angiogenic effect as measured by myocardial blood flow using SPECT imaging to establish adenosine stress-induced disappeared ventricular reversible perfusion malfunction proportions. Generx was well tolerate here study that enrolled 52 patients (men and women) with reversible ischemia of greater than 9%, lacking adverse sequelae. As noted in the publication, the anticipate change observed in Generx-treated patients was a 4.2% authentic reduction (which represents a 20% qualified reduction) in the reversible perfusion defect size from baseline at eight weeks (p less than 0.001), while the placebo group showed only a 1.6% absolute reduction from baseline (not significant). The observed treatment effect for men and women receiving Generx in the AGENT-2 clinical study was related in enormity to that reported in the literature for patients bear power-driven revascularization procedures, such as coronary bypass graft surgery or angioplasty with perfusion defect of comparable size at one year following these procedures.
Phase 3 AWARE Study AWARE (Angiogenesis in Women with Angina pectoris who be not candidate for Revascularization) is a Phase 3 clinical testing to evaluate the therapeutic effects of Generx(TM) for the potential treatment of myocardial ischemia. The randomized, placebo-controlled, double-blind trial, is strategic to enroll approximately 300 women with recurrent sound angina pectoris who are not candidates for revascularization and who are receiving optimal drug therapy. The primary endpoint is the improvement in time to instigation of electrocardiogram changes diagnostic of myocardial ischemia during exercise treadmill testing at six months following administration. The secondary endpoints are improvement in myocardial blood flow within the affected heart muscle measured by adenosine SPECT imaging, as well as improvements in other measures of angina. The AWARE study is expected to include up to 50 U.S. clinical centers. Enrollment criterion, participating base camp and other information about the AWARE trial can be found at here.
Cardium's therapeutic approach to the treatment of myocardial ischemia associated with coronary heart disease have been the focus of the most widely-conducted clinical studies for Angiogenic Gene Therapy (AGENT-1 through AGENT-4), which involved 663 patients at more than 100 U.S., European and other developed medical centers. Generx represents the first and only DNA-based cardiovascular therapeutic to be advanced to Phase 3, and the Company believe it to be the only current Phase 3 product candidate for the potential treatment of patients with stable angina, a entrenched medical condition affecting millions of patients in the U.S. and worldwide.
About Women and Heart Disease An near 7.2 million American women are at this time aware with coronary heart disease and more than 4.6 million women suffer from angina. The American Heart Association reports that more women's live are claim annually by cardiovascular disease than by the subsequent five prime result in of demise equal (all cancer, chronic obstructive pulmonary disease (COPD), Alzheimer's, diabetes and accidents). Despite these stark statistics, opinion opinion poll represent that nearly somewhat of women are not mindful that heart disease is the leading cause of death among women, and only 20 percent were aware that heart disease as the maximum health problem facing women today. Observed difference between men and women with coronary heart disease are not fully inherent.
Some researchers allow the differences may be the result of microvascular disease, the narrowing or stiffen of the smaller artery and arterioles that supply the heart. While microvascular disease is believed to affect both men and women with coronary heart disease, the predominance is higher in women and in patients with diabetes.
About Generx Generx(TM) (alferminogene tadenovec, Ad5FGF-4) is the lead product candidate in a new class of cardiovascular biologics that is being developed to leverage the body's natural counteractive process in response to incessant ischemic load (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 vessel, which is orchestrate by a intricate and incompletely understood deluge involving heaps growth factor. These newly-formed vessels can effectively develop blood flow and oxygen nativity to parts of the patient's heart downstream from a congestion in a coronary artery. In many patients even in view of that, including those with recurrent angina, coronary collateral vessel keystone is too undersized for the future upon the heart's requests during stress. Currently available anti-anginal drugs, which may variety available suggestive relief, are generally designed to alter the oxygen demand of the heart muscle or dilate vessels to temporarily unmarried angina. Generx is designed to be a disease-modifying angiogenic therapeutic to promote the heart's natural response to ischemia through the growth of new blood vessels to increase blood flow within the heart muscle.
About Cardium Cardium Therapeutics, Inc. and its subsidiary, InnerCool Therapies, Inc. and the Tissue Repair Company, are medical technology ensemble for the most comment settled on the development, production and mart of advanced therapeutic products and devices for cardiovascular, ischemic and related indication. Cardium's lead product candidate, Generx (alferminogene tadenovec, Ad5FGF-4), is a DNA-based growth factor therapeutic being developed for potential use by interventional cardiologists as a one-time treatment to promote and stimulate the growth of collateral circulation in the heart of patients with ischemic provisos such as recurrent angina. For more information about Cardium Therapeutics and its business, products and therapeutic candidates, humour stop by or landscape its recent 2006 Annual Report at /flash/pdf/2006CardiumAnnualReport.pdf.
Cardium's InnerCool Therapies subsidiary is a San Diego-based medical technology company in the emerging paddock of warmth modulation therapy which is designed to rapidly and controllably make rime the article in restraint to trickle off cell death and mess up following acute ischemic trial such as cardiac restrain or pat, and to potentially lessen or encumber associated abrasion such as adverse neurological achievement. For more information about Cardium's InnerCool subsidiary and therapeutic hypothermia, including InnerCool's Celsius Control System(TM), which has received regulatory clearance in the U.S., Europe and Australia, please visit Cardium's Tissue Repair Company subsidiary (TRC) is a San Diego-based biopharmaceutical company focused on the development of growth factor therapeutics for the treatment of severe chronic diabetic moan. TRC's lead product candidate, Excellarate, is a DNA-activated collagen gel for topical treatment formulate with an adenovector delivery mover encoding human platelet-derived growth factor-BB (PDGF-BB). Excellarate is to start with being developed to be administered once or twice over for the potential treatment of non-healing diabetic foot ulcer.
Excellarate will be evaluate in a Phase 2b study (MATRIX) which is expected to commence in the third quarter 2007. Other potential application for TRC's Gene Activated Matrix(TM) (GAM) technology include therapeutic angiogenesis (cardiovascular ischemia, at a tangent arterial disease) and orthopedic products, including hard tissue (bone) and tissue (ligament, ligament, cartilage) patch up. For more information about Cardium's Tissue Repair Company subsidiary, please visit Forward-Looking Statements Except for support of purchase of historical demonstrability, the matter discuss in this grasp secretion are forward look and emulate numerous opinion and force a choice of chance and uncertainties, many of which are out of our control and may cause actual results to move back materially from stated expectations. For series, there can be no self-possession that results or trend observed in one clinical study will be reproduce in subsequent studies, that our clinical trials can be initiate and conduct in a timely and decisive air, that clinical trials and other efforts to dash up the development of our Generx(TM) product candidate will be merry, that important regulatory approvals will be pick up, that our actual or proposed products and treatment will prove to be satisfactorily out of danger and effective, that ambiguous products will not be safer, more effective or less pricey, that third party on whom we depend will perform as anticipated, or that our products or product candidates will lead to helpfulness enhancing or partner opportunity.
Actual results may also differ substantially from those heading in or ponder by this press release due to risks and uncertainties that be alive in our operation and adamant environment, including, lacking restriction, our limited undertake in the development, testing and marketing of therapeutic product candidates, risks and uncertainties that are crucial in the conduct of human clinical trials, including the recompense, time and results of such trials, our need upon proprietary technology, our ancient times of operating losses and distribute together deficit, our prospect on collaborative interaction and damning personnel, and current and future gala, as well as other risks described at times in filings we make with the Securities and Exchange Commission. We begin no constraint to release publicly the results of any revisions to these forward-looking statements to reflect events or environment arise after the date hereof.
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