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Positive Phase III Results Reported for Angiogenic Gene Therapy in Patients With Myocardial Ischemia

Generx promotes growth of microvascular circulation in the heart

Promising phase III results have been reported with Generx (Ad5FGF-4, alferminogene tadenovec), an angiogenic gene therapy candidate, in patients with myocardial ischemia due to coronary artery disease (CAD). The new data were presented June 24 at the Biotechnology Industry Organization’s 2014 BIO International Convention, held in San Diego, California.

According to the product’s developer (Cardium Therapeutics), Generx is designed to be administered one time by an interventional cardiologist on an outpatient basis during a brief angiogram-like procedure using a standard balloon catheter.

Generx promotes the growth of microvascular circulation in the heart, thereby enhancing cardiac perfusion. It is intended as a treatment for patients with myocardial ischemia and persistent angina pectoris due to CAD despite optimal medical therapy and bypass surgery or percutaneous coronary intervention (PCI).

In addition, the treatment could potentially benefit patients who are diagnosed with cardiac microvascular insufficiency (defined as myocardial ischemia without large-vessel disease sufficient to cause ischemia), according to Cardium. This group of patients is not helped by bypass surgery or PCI because these techniques are applicable only to identifiable and treatable lesions in large vessels and not to the growth of smaller vessels.

The primary efficacy endpoint in the phase III ASPIRE study was the improvement in myocardial perfusion, as measured by changes after 8 weeks in the reversible perfusion defect size (RPDS).

After 8 weeks, treatment with Generx resulted in a 24% improvement in RPDS — a statistically significant response compared with the control group (n = 11; P = 0.01). This improvement was consistent with the improvement in RPDS reported in a previous phase II study of Generx, published in 2003.

Generx is a gene therapy construct that uses an adenovirus serotype 5 delivery vector, which drives short-term, transient expression of the fibroblast growth factor-4 (FGF-4) transgene. It is designed to stimulate the body’s natural healing response to ischemic CAD by promoting microvascular angiogenesis and arteriogenesis, and by enhancing cardiac perfusion.

When administered into the coronary arteries under transient ischemic conditions, Generx distributes into the heart’s microvascular pathways and transfects heart cells by binding to cell-surface coxsackievirus–adenovirus receptors (CARs). CARs are found throughout the surface area of the heart. The binding affinity of Generx for CAR receptors is enhanced by the induction of transient ischemia and by the use of agents such as nitroglycerin to boost cell permeability during administration. The transfected heart cells then express and release FGF-4 protein, which promotes the growth of new blood vessels, thereby increasing blood flow to ischemic heart tissue.

Source: Cardium Therapeutics; June 24, 2014.

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