Today before the opening bell, Cardium Therapeutics announced its Chief Scientific Officer, Gabor M. Rubanyi, M.D., Ph.D. delivered a presentation at the 2013 Phacilitate Annual Cell & Gene Therapy Forum in Washington, DC. The presentation, titled “Optimizing Phase III Trial Design for Generx® (Ad5FGF-4),” outlined the current scientific knowledge about the mechanistic basis of adaptive coronary collateral growth, the biological processes to be targeted by therapeutic angiogenesis, and the lessons learned during the past decade of the company’s Generx clinical development program.
If you would like to view the presentation, visit http://www.cardiumthx.com/generx.html.
“The presentation yesterday reviewed new techniques that have been implemented to optimize our international Phase 3 ASPIRE clinical study for the Company’s Generx® (Ad5FGF-4) DNA-based angiogenic growth factor drug candidate, including: (1) diagnostic identification of patients likely to be more responsive to angiogenic therapy; (2) new balloon catheter-based delivery methods designed to boost adenovector gene delivery and enhance angiogenic growth factor efficiency; and (3) selection of relevant clinical endpoints which may be useful in future clinical studies and help advance the field of therapeutic angiogenesis,” stated Christopher J. Reinhard, Cardium’s Chairman and CEO.
Generx is an interventional cardiology-focused product candidate that is being developed to offer a one-time, non-surgical option for the treatment of a medical condition termed cardiac microvascular insufficiency (CMI) in patients with myocardial ischemia and symptomatic chronic stable angina pectoris due to coronary artery disease. Patients with CMI have had an insufficient angiogenic response to their current disease state and may benefit from a biological therapy that enhances cardiac perfusion through the facilitation of collateral vessel formation. Currently, patient inclusion in the ASPIRE study requires evidence of stress induced reversible myocardial ischemia as measured by SPECT imaging. The goal of the company’s Generx product candidate is to improve blood flow to the heart muscle by promoting and enhancing cardiac perfusion through the enlargement of pre-existing collateral arterioles (arteriogenesis) and the formation of new capillary vessels (angiogenesis). Various catheter-based imaging diagnostics including fractional flow reserve and washout collaterometry could enhance the clinical adoption of this non-surgical therapeutic angiogenesis approach following initial registration.
Cardium’s extensive preclinical and clinical studies have been instrumental in identifying cardiac ischemia as a key facilitator of non-surgical DNA-based angiogenic therapy. Improved adenovector administration methods combine non-surgical, percutaneous balloon catheter-based delivery to transiently induce ischemia together with the use of nitroglycerin to enhance vector uptake. By increasing cell transfection efficiency and reaching both the peri-ischemic regions and pre-existing collaterals in the heart, this modified approach offers the potential to effectively simulate both angiogenesis and arteriogenesis to bring about improved blood flow. Cardium’s new delivery techniques are also designed to provide uniform Generx uptake, to reduce response variability and to allow for the potential treatment of patients with a broader range of associated coronary artery disease.
Cardium has modified the primary endpoint of the ASPIRE clinical study from the traditional measure of improvement in treadmill exercise time (ETT) to a more objective efficacy endpoint of reduction in reversible perfusion deficit based on SPECT myocardial perfusion imaging. Similar to mechanical/surgical cardiac revascularization approaches, the goal of Generx treatment is to improve myocardial perfusion (blood flow). SPECT myocardial perfusion imaging can be used to quantitatively evaluate Generx’s effectiveness by measuring improved myocardial blood flow under stress, a key prognostic indicator that is associated with the regenerative process of new collateral vessel formation in and around the regions of ischemia. While walking time during ETT has been a traditional efficacy measure of anti-anginal drugs, it is based on a subjective assessment of chest pain (angina pectoris), does not directly measure improvements in cardiac blood flow, and can be affected by other variables.
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 patients following a single intracoronary infusion as measured by the objective efficacy endpoint of SPECT imaging. 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.
For more information, visit www.CardiumTHX.com
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