Cardium Therapeutics today reported on new insights and confirmatory preclinical study results on the Generx (Ad5FGF-4) angiogenic therapy product candidate based on the Company’s sponsored research conducted at Emory University. The findings, which provide further support for the apparent safety and effectiveness of Generx as a potential one-time non-surgical approach to the treatment of coronary heart disease, are being presented at the Phacilitate Annual Gene and Cell Therapy Forum held January 30 – February 1, 2012 in Washington, DC.
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The recent preclinical findings demonstrate that induced transient ischemia, using a standard angioplasty balloon catheter, combined with the intracoronary co-infusion of nitroglycerin, substantially enhanced adenovector-mediated gene delivery to the heart. These findings have been incorporated into the protocol for the planned 100-patient Generx (Ad5FGF-4) ASPIRE Phase 3 registration study which, as previously reported, is expected be initiated in the first quarter 2012. The YouTube video “Cardium Generx Cardio-Chant” provides an overview of the Company’s Generx (Ad5FGF-4) product candidate, at http://www.youtube.com/watch?v=pjUndFhJkjM.
The new data underscore the expected benefit of Cardium’s improved adenovector administration methods that combine non-surgical, percutaneous balloon catheter-based delivery with transiently-induced ischemia and nitroglycerin to enhance uptake leading to improved microvascular circulation in the heart. By increasing cell transfection efficiency, this modified approach allows for effectively obtaining additional targeted expression of growth factors within the ischemic heart, where the resulting angiogenesis or blood vessel growth can bring about improved blood flow throughout the ischemic myocardium. Traditional interventional cardiology approaches such as coronary artery bypass surgery (CABG) or angioplasty and stenting (PCI), not only require invasive and costly surgical procedures but they can only directly target selected vulnerable spots in larger vessels that are susceptible to treatment and reachable through mechanical intervention.
Another important outcome of these preclinical studies was the confirmation that intracoronary infusion of an adenovector directly to the ischemic region of the left ventricle caused no myocardial inflammation or any other untoward effects. These Cardium-sponsored studies were undertaken by researchers at the Carlyle Cardiothoracic Surgery Center at Emory University, Atlanta. The presentation given at the Annual Gene and Cell Therapy Forum entitled “ASPIRE Trial: A Phase 3 Pivotal Registration Trial Incorporating Preclinical and Clinical Lessons Learned in the Past Decade”, is now available for viewing on the Generx section of Cardium’s website at http://www.cardiumthx.com/generx.html.
“Cardium has established the world’s largest clinical database on a DNA-based interventional cardiovascular therapeutic derived from clinical studies in over 650 patients with coronary artery disease that have been conducted at over 100 medical centers in the United States, South America and Western Europe. Our extensive preclinical and clinical studies have also identified cardiac ischemia as a key factor for the successful use of non-surgical DNA-based angiogenic therapy. The observation that myocardial ischemia is a necessary condition for both the effective delivery and therapeutic effectiveness of Generx is a very positive one, and has favorable implications for the potential utility of Generx in the treatment of coronary heart disease. The new findings confirming that our modified delivery procedures have the potential to substantially improve adenovector uptake further support the expected value of our ASPIRE Phase 3 registration study, which employs these techniques in targeted patients with coronary artery disease who have the potential to be best served by our Generx angiogenic therapy,” stated Christopher J. Reinhard, Cardium’s Chairman and Chief Executive Officer.
Generx ASPIRE Clinical Study
The Company has received clearance from the Russian Ministry of Health and Social Development to commence a Phase 3 registration study for the Company’s Generx™ (alferminogene tadenovec, Ad5FGF-4) biologic product candidate, which is expected to begin patient enrollment in the first quarter 2012. Generx is a new and innovative DNA-based angiogenic therapy designed for the potential treatment of myocardial ischemia due to coronary artery disease. The Russian Health Authority has assigned Generx the therapeutic drug trade name of Cardionovo™ for marketing and sales in Russia.
This newly approved clinical study (ASPIRE) is a randomized, controlled, parallel group, multi-center study designed to evaluate the safety and efficacy of Cardium’s Generx product candidate using SPECT imaging to measure improvements in microvascular cardiac perfusion following a one-time, non-surgical, catheter-based administration of Generx DNA-based angiogenic therapy. As designed, the ASPIRE clinical study is expected to enroll approximately 100 men and women with myocardial ischemia due to coronary artery disease at up to six leading medical centers in Moscow. The study’s primary efficacy endpoint will be the improvement in reversible perfusion defect size as measured by SPECT imaging.
The ASPIRE study will represent the fifth clinical study under Generx’s clinical development program that when completed will have enrolled more than 750 patients at over 100 medical centers throughout the U.S., Canada, South America, Western Europe and Russia. Based on the specified clearance for the Russian Health Authority, with positive safety and efficacy data from this single registration study, Cardium’s Russian sponsor and development partner, Advanced Biosciences Research, an affiliate of the contract research organization bioRASI, would be in a position to consider the submission of an application for marketing and sales of Generx in the Russian Federation, and to advance forward with applications and submissions seeking approval for marketing and sales of Generx in certain other countries of the Commonwealth of Independent States, comprising former republics under the Soviet Union. The ASPIRE study could also provide additional clinical evidence regarding the safety and effectiveness of Generx that would be useful for optimizing and broadening commercial development pathways in other industrialized countries.
Positive results from the prior Phase 2a clinical study (Grines et al., J Am Coll Cardiol 2003; 42:1339-47) showed that Generx improved myocardial blood flow in the ischemic region of the hearts of men and women following a single intracoronary infusion as measured by the objective efficacy endpoint of SPECT imaging. 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) at eight weeks following treatment. The observed treatment effect for patients receiving Generx was similar in magnitude to that reported in the literature for patients undergoing angioplasty/stent or revascularization procedures with reversible perfusion defects of comparable size at one year following these procedures.
An independent long-term prospective study published in 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 showed that long-term cardiac mortality was approximately 66% lower in patients with a highly developed collateral vessel blood supply (p=0.019). For the first time, this study showed the importance of collateral circulation beyond simply the relief of angina and provided further support of the potential for long term benefits from angiogenic therapy.
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