CARDIOVASCULAR DISEASE
Cardiovascular diseases represent the leading cause of death in the United States and in most Western countries. Cardiovascular disease refers to the class of diseases that involve the heart or blood vessels. Peripheral arterial disease, or PAD, including critical limb ischemia, or CLI, and Coronary Artery Disease, or CAD, also known as ischemic heart disease, or IHD, are the end result of arterial occlusive disease, which is most commonly known as atherosclerosis. Atherosclerosis affects only the inner lining of an artery and is characterized by fatty deposits that block the flow of blood.
PAD is caused by atherosclerosis in association with hypertension, hypercholesterolemia, cigarette smoking and diabetes. PAD is a common circulatory problem in which narrowed arteries reduce the blood flow to the limbs. Early symptoms of PAD include transient pain in the legs upon walking, a condition called intermittent claudication, which is caused by ischemia. Approximately 25% of ischemic patients will progress to develop CLI, which is associated with pain at rest and ulcers, and frequently requires amputation. Altogether approximately 30% of patients with PAD die within 5 years of developing PAD, rising to approximately 50% after 10 years, and representing a mortality rate exceeding most other conditions including CAD and breast cancer. The number of therapeutic options for PAD remains very limited in comparison with other areas of cardiovascular medicine. The healthcare burden associated with PAD-related amputations in the United States is estimated to be greater than $10 billion per year.
CAD occurs when the coronary arteries that supply blood to the heart muscle become hardened and narrowed. CAD is the most common type of heart disease and is the leading cause of death in the U.S. in both men and women. Over time, CAD can weaken the heart muscle and contribute to heart failure or arrhythmias. Current treatment regimens for CAD include drugs, catheter-based interventional therapies such as balloon angioplasty or stents, mechanical therapies such as atherectomy, and bypass surgery.
We believe, PAD and CAD, may be better treated with angiogenesis, which refers to the growth of new blood vessels from pre-existing vessels to replace those blocked by the disease. Our core DNA delivery technology may allow the targeted delivery of certain growth factors with potential therapeutic value in the emerging field of angiogenesis. Angiogenesis has been shown to occur by the exogenous administration of angiogenic growth factors. We believe that the localized and sustained expression of these growth factors from plasmids may be both safe and effective.
Sanofi-aventis and AnGes MG have applied our technologies to the local and sustained delivery of genes that encode angiogenic growth factors which promote the growth of blood vessels. Patients suffering from peripheral vascular disease may avoid amputation of limbs succumbing to restricted blood flow.
AnGes stopped its Phase 3 trial in June 2007 after an interim analysis on the first 41 patients showed that the primary efficacy endpoint in the trial had been achieved with statistical significance and that there were no major safety concerns related to treatment. On the basis of these data, AnGes filed a New Drug Application in March 2008 for marketing approval of its Collategene™ angiogenesis product for PAD and Buerger's disease in Japan.
Sanofi-aventis started a 500-patient Phase 3 trial in late 2007 and expects to file for marketing approval in 2010.