Cardium Therapeutics today announced the initiation of the ASPIRE Phase 3 registration study to evaluate the therapeutic effects of Cardium’s lead product candidate, Generx® (Ad5FGF-4) in patients with myocardial ischemia (insufficient blood flow in the heart due to coronary artery disease).
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The ASPIRE study is a 100-patient, randomized and controlled multi-center study being conducted at up to six leading cardiology centers in the Russian Federation. The study is designed to further evaluate the safety and effectiveness of Cardium’s Generx DNA-based angiogenic product candidate, which has already been tested in clinical studies involving 650 patients at more than one hundred medical centers in the U.S., Europe and elsewhere. The therapeutic efficacy of Generx will be quantitatively assessed using rest and stress SPECT imaging (Single-Photon Emission Computed Tomography) to sensitively measure improvements in microvascular cardiac perfusion following a one-time, non-surgical, catheter-based administration of Generx. The Cedars-Sinai Medical Center Nuclear Cardiology Core Laboratory in Los Angeles, California, will serve as the central core lab for the ASPIRE study and will be responsible for the analysis of SPECT myocardial imaging data electronically transmitted from the Russian medical centers participating in the ASPIRE study. Advanced Biosciences Research, an affiliate of bioRASI which is a global clinical research organization, is Cardium’s Russian sponsor and development partner and is responsible for the ASPIRE program management and regulatory compliance.
Generx is a disease-modifying regenerative medicine biologic that is being developed to offer a one-time, non-surgical option for the treatment of myocardial ischemia in patients with stable angina due to coronary artery disease, who might otherwise require surgical and mechanical interventions, such as coronary artery by-pass surgery or balloon angioplasty and stents. Similar to surgical/mechanical revascularization approaches, the goal of Cardium’s Generx product candidate is to improve blood flow to the heart muscle – but to do so non-surgically, following a single administration from a standard cardiac infusion catheter. Additional information about Generx and the ASPIRE study is available in a presentation titled “Generx Angiogenic Therapy: Regenerative Medicine for Interventional Cardiology” at http://phx.corporate-ir.net/phoenix.zhtml?c=77949&p=irol-presentations, and at http://clinicaltrials.gov/ct2/show/NCT01550614?term=cardium&rank=1. The YouTube video, “Cardium Generx Cardio-Chant” is at http://www.youtube.com/watch?v=pjUndFhJkjM.
“The ASPIRE trial represents a major milestone for Cardium and is 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. With positive safety and efficacy data from this single registration study, a Generx clinical dossier would become eligible for submission for marketing and sales in the Russian Federation, and would also be expected to support 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,” stated Christopher J. Reinhard, Cardium’s Chairman and Chief Executive Officer.
The ASPIRE study is also specifically designed to 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 such as Brazil, India, Europe and the United States.
Generx Clinical Development
The ASPIRE study (A Randomized, Controlled, Parallel Group, Multi-center Study To Evaluate The Efficacy And Safety Of Ad5FGF-4 Using Adenosine SPECT Myocardial Perfusion Imaging In Patients With Stable Angina Pectoris) 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 primary efficacy endpoint of the study will be the improvement in reversible perfusion defect size as measured by SPECT myocardial perfusion imaging both at rest and under cardiovascular stress. The Russian Health Authority has assigned Generx the therapeutic drug trade name of Cardionovo™ for marketing and sales in Russia.
SPECT myocardial perfusion imaging can be used to quantitatively evaluate the therapeutic efficacy of Generx by measuring improved myocardial blood flow under stress; it is also a key prognostic indicator of future cardiovascular events. Generx may improve myocardial blood flow during stress – a change that is associated with the regenerative process of new collateral vessel formation in and around regions of ischemia. The Cedars-Sinai Core Laboratory was previously responsible for the data management, evaluation and interpretation of a successful Generx Phase 2 clinical study that also used SPECT myocardial perfusion imaging as the primary endpoint measure. Positive results from this Phase 2 clinical study (Grines et al., J Am Coll Cardiol 2003; 42:1339-47) showed that Generx could improve myocardial blood flow in the ischemic region of the hearts of patients following a single intracoronary infusion, as measured by SPECT imaging. The observed treatment effect (reduced reversible perfusion defect size) for patients receiving Generx was similar in magnitude to that reported in the literature for patients undergoing angioplasty/stent or surgical revascularization procedures.
Recent data from preclinical research conducted at Emory University provided 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. This important study demonstrated that induced transient ischemia, using a standard angioplasty balloon catheter, combined with intracoronary co-infusion of nitroglycerin, substantially enhanced adenovector-mediated gene expression in the heart. Use of these newly applied gene transfer techniques increased the efficiency of gene transfer in preclinical studies by more than two orders of magnitude (p<0.001). These findings have been incorporated into the protocol for the ASPIRE study and the new data underscore the expected benefit of Cardium’s improved adenovector administration methods. Use of combined non-surgical, percutaneous balloon catheter-based delivery with transiently-induced ischemia and nitroglycerin to enhance uptake is expected to lead to improved microvascular circulation in the heart. By increasing gene transfer efficiency, this modified delivery approach allows for maximizing targeted expression of FGF-4 protein within the ischemic heart of all treated patients, where the resulting angiogenesis or blood vessel growth can bring about improved blood flow. Traditional interventional 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. The recent data, which were presented at the 2012 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,” can be viewed at http://www.cardiumthx.com/generx.html.
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