Angiogenic gene therapy shows promise in phase III SPECT study

Taxus Cardium Pharmaceuticals Group have announced encouraging interim phase III cardiac SPECT imaging results from the international ASPIRE (Efficacy and Safety of Ad5FGF-4 for Myocardial Ischemia in Patients With Stable Angina Due to Coronary Artery Disease) trial. Generx Ad5FGF-4 is a potential angiogenic gene therapy for the development of new vascularization. The data was presented June 24 during the 2014 BIO International Convention in the company’s home base of San Diego.

An estimated 100 subjects received either Generx or a control in this randomized international trial. Stress myocardial perfusion was seen as inadequate for all patients at baseline. Eight weeks after receiving the one-time interventional therapy or control, those who received Generx were shown to have significantly better blood flow under stress comparable to more conventional treatments such as bypass surgery or angioplasty.

The ASPIRE clinical study is the fifth Generx gene therapy trial representing data from 780 patients treated in more than 100 institutions across the United States, Canada, South America, Western Europe and Russia.

SPECT imaging was assessed by the Nuclear Cardiology Core Laboratory at Cedars-Sinai Medical Center in Los Angeles. Results after eight weeks showed that Generx treatment led to a 24 percent improvement in reversible perfusion defect size (RPDS).

"The new data from the international phase III ASPIRE clinical study further supports findings of safety and efficacy from the four prior and published Generx angiogenic gene therapy (AGENT) clinical studies that have been conducted at over 100 medical centers worldwide. This represents another important step forward in the development of an innovative biology-based microvascular gene therapy tool for the interventional cardiologist designed to broaden the cycle of care for a large number of patients worldwide with myocardial ischemia," said Timothy Henry, MD, chief of cardiology at the Cedars-Sinai Heart Institute, in a press release.

A pooled analysis of the two trials showed a 25 percent total improvement in RPDS. The current ASPIRE trial is scheduled to continue until December of this year.

The primary mechanism of the Generx alferminogene tadenovec therapy is the use of adenovirus serotype 5 delivery vector for short-term transient expression of the Fibroblast Growth Factor-4 (FGF-4) transgene. Generx is aimed toward patients with myocardial ischemia and persistent angina pectoris (chest pain), due to coronary artery disease, who have already received conventional first-line treatments with surgical bypass or percutaneous coronary intervention (PCI). Patients with cardiac microvascular insufficiency may also benefit from this gene therapy.

An article by Cardium’s chief scientific officer, Gabor M. Rubanyi, MD, PhD, titled  "Identifying and overcoming obstacles in angiogenic gene therapy for myocardial ischemia," is expected to come out soon in the Journal of Cardiovascular Pharmacology.