Cardium Therapeutics has announced the publication of a review article in the Journal of Cardiovascular Pharmacology that concludes a gene therapy product promoting the growth of blood vessels is “highly warranted” to treat about one million US heart-disease patients and six million more worldwide who are either ineligible or poor candidates for traditional angioplasty, stent placement or bypass surgery.
The review described significant progress in gene therapy that resulted from optimised techniques to deliver an effective vessel-growth-promoting gene to heart tissue of patients most likely to respond to such treatment, and was authored by Gabor M Rubanyi, chief scientific officer of Cardium Therapeutics. Using Cardium’s cardiovascular gene therapy, researchers have quantified significant improvements in cardiac blood flow in treated patients with 3D visualisation scans.
Rubanyi says improvements have been incorporated into the delivery of Cardium’s Generx product candidate in the ASPIRE phase 3 gene therapy clinical study, which is currently underway in the Russian Federation.
“While the basic science was never in doubt, more than two decades of refinements were needed to develop a safe, effective and optimised gene therapy for coronary artery disease patients who do not have other good treatment options,” Rubanyi says.
Growth of collateral coronary vessels is a natural response to chronic myocardial ischaemia, or restricted blood flow in the heart. However, Rubanyi says up to 70% of patients with advanced coronary artery disease fail to grow collateral vessels, or develop too few to significantly increase blood flow. Furthermore, no current treatment options stimulate the growth of collateral vessels in these patients.
In two earlier clinical trials of Cardium’s Generx product candidate, improved exercise tolerance test (ETT) performance on treadmills was used as the endpoint. In ETT tests, patients rely on their individually subjective discomfort levels to decide when to step off the treadmill. However, treadmill test results vary for a given patient from day to day. Placebo effects in control patients can be significant, and results also vary depending on participants’ fluctuating disease symptoms or complications of unrelated prescription medications.
A clinical trial of Generx conducted by Schering AG Germany and Berlex Laboratories in the United States, with whom Rubanyi was associated, employed a more sensitive and relevant endpoint: increased perfusion of blood in the heart eight weeks after treatment – as measured by the FDA-validated and widely used single photon emission computed tomography (SPECT) imaging system. Cardium has based its current international Phase 3 clinical trial on the SPECT endpoint, with results being evaluated by one of the world’s top cardiovascular imaging centres, the Nuclear Cardiology Core Laboratory at Cedars-Sinai Medical Center in Los Angeles. Following regulatory approval, it is not expected that SPECT would be required, and Generx would be administered to patients during a standard angiogram-like procedure.
“With significant improvements in gene therapy delivery, more relevant assessment of treatment and selection of patients who are likely responders, we have finally overcome the main obstacles to clinical success,” Rubanyi says.