Generx represents a new class of therapeutic designed to address a large and unmet medical need among patients with heart disease. It is estimated that 12% of patients with obstructive coronary artery disease continue to experience angina because their underlying medical condition is not fully addressed or cannot be resolved by chronic drugs or surgical/mechanical interventions. In addition, a recent meta-analysis reported that approximately 20% of patients who have a coronary angiography due to ongoing angina do not have obvious large vessel disease, a condition generally referred to as Cardiac Syndrome X, many of whom are presumed to have coronary disease that is diffuse and/or affects smaller vessels within the heart that are not reachable through surgical intervention.
Myocardial ischemia, including that associated with CMI, can be effectively diagnosed and its potential treatment quantified using SPECT imaging (Single-photon emission computed tomography). SPECT has both diagnostic and prognostic value in the management of patients with coronary artery disease because it identifies and quantitatively measures regions of the heart muscle that are at greatest risk during periods of ischemia, such as that brought on during exertion.
Generx is designed to be a one-time non-surgical treatment that may help many of such patients by directly addressing their underlying microvascular angina, as well as providing a non-surgical option for patients in whom coronary intervention is either contraindicated or not desirable.
Taxus Cardium researchers believe that biologically enhanced perfusion through microvascular gene therapy offers the opportunity to reduce angina attacks and improve quality of life for patients with advanced CMD. An independent long-term (10 year) study showed that having high levels of microvascular (collateral) perfusion may also be cardio-protective and improve outcomes following a major adverse cardiac event. The Company’s initial clinical research is focused on enhancing microvascular perfusion as a therapy for myocardial ischemia that causes angina pectoris, but also plans to evaluate patients through a registry following initial registration for marketing and sales to evaluate the medical utility of the Generx product candidate to improve mortality outcomes following major serious adverse cardiac events.
Following a one-time, non-surgical, intracoronary catheter-based delivery by an interventional cardiologist in a routine out-patient procedure (that is very similar to an angiography procedure), Generx is designed to transfect heart cells by binding to cell surface Coxsackievirus-Adenovirus Receptors, and drive the localized, short-term cellular expression of FGF-4 protein, which in turn stimulates the release and action of other key growth factors to orchestrate and promote the growth of cardiac microvascular circulation (functional collateral network) in ischemic cardiac tissue. This process is believed to enlarge pre-existing collateral arterioles (arteriogenesis) and form new capillary vessels (angiogenesis). An independent long-term prospective study has demonstrated the importance of collateral circulation beyond simply the relief of angina and provided further support of the potential for long term benefits from Generx therapy.
Upon the successful completion of the ongoing ASPIRE international clinical study, Generx will have been the subject of five randomized and controlled multi-center clinical studies involving approximately 750 patients at over 100 medical centers in the United States, Canada, Western Europe, South America and the Russian Federation. The combined data will represent one of the largest clinical and regulatory dossiers of regenerative gene therapy in the world, and is designed to establish Generx as safe and well tolerated and capable of improving myocardial perfusion in patients with myocardial ischemia due to advanced coronary artery disease. This extensive clinical experience has enabled optimization of Generx administration procedures and uptake (e.g. by induction of transient ischemia during infusion), and identification of quantifiable parameters for patient selection and treatment outcomes (e.g. SPECT imaging), lessons incorporated into the ASPIRE trial design.
- For patients with Cardiac Microvascular Insufficiency (CMI) or those not suitable for surgical revascularization
- Non-invasive, quantitative SPECT perfusion imaging used to identify treatment candidates and as clinical efficacy endpoint
- Transient ischemia during Ad5FGF-4 catheter-based infusion improves DNA uptake
- Generx-mediated FGF-4 expression promotes the growth of a functional collateral network in ischemic cardiac tissue
- Safe and effective, with potential for long-term benefits to patients with angina pectoris due to CMD in association with advanced coronary artery disease
Upon completion of the ASPIRE study, Taxus Cardium plans to meet with the U.S. FDA to harmonize design of the ASPIRE trial with that of the U.S. registration trial.