Corautus' technology is currently being tested in a randomized, double-blinded, dose-ranging and placebo-controlled Phase IIb clinical trial known as GENASIS ("Genetic Angiogenic Stimulation Investigational Study"), which will enroll 404 patients with Class III or IV angina that are not suitable candidates for traditional revascularization procedures. The GENASIS trial will be conducted in approximately 25 cardiac medical centers throughout the United States. In the GENASIS trial, defined doses of VEGF-2 in the form of "naked" plasmid DNA are delivered to diseased heart muscle tissue via the Boston Scientific Corporation (NYSE: BSX) Stiletto(TM) endocardial direct injection catheter system. The injection procedure is performed by a cardiologist in a standard cardiac laboratory. Corautus expects to complete patient enrollment of the Phase IIb trial around the end of 2005.
Dr. Douglas W. Losordo, the national Principal Investigator for the GENASIS trial and Chief of Cardiovascular Research at Caritas St. Elizabeth's Medical Center in Boston, commented, "While previous findings showed positive results, the two year follow-up of the Phase I data demonstrate that VEGF-2 therapy may be associated with prolonged clinical benefit in patients who have no other options for the treatment of severe angina. These results are cause for encouragement, and we are now conducting the largest double-blinded, placebo-controlled trial of its kind to confirm these findings."
Dr. Richard A. Schatz, Co-Chairman of the Division of Cardiology and Research Director of Cardiovascular Interventions at Scripps Clinic's Heart, Lung and Vascular Center in San Diego, stated, "Because this patient population has no available treatment options, they are frequently incapacitated with chest pain and are unable to live a normal life. Guided by the positive trends in the earlier Phase I and IIA trials, we are now studying the safety and efficacy of VEGF-2 in a statistically significant, double blinded, randomized, placebo controlled trial. If the early findings are repeated in the GENASIS trial, VEGF-2 treatment may result in a new class of therapeutics for the treatment of refractory angina."
Richard E. Otto, President and CEO of Corautus, stated, "The long-term findings being reported in the Journal of Interventional Cardiology this month are consistent with the one year follow-up results previously reported by investigators. The current GENASIS trial is designed to continue the clinical safety and efficacy study in a larger number of patients. The VEGF-2 is administered for the treatment of severe angina in a patient population that has exhausted current treatment options. We are fortunate to have the interest and participation of many of the leading cardiologists across the United States, including Drs. Losordo and Schatz."
About the Phase I Trial
Corautus (through its wholly-owned subsidiary, Vascular Genetics Inc.) conducted a Phase I multi-center trial that enrolled 30 patients with Class III or IV angina refractory to medical therapy who also had multivessel occlusive coronary artery disease not amenable to revascularization. Patients were treated in dose-escalating fashion at 200, 800 or 2,000 mg dose, injected directly into the heart muscle with a hypodermic needle after a mini-thoracotomy, a surgical incision in the chest wall.
Patients were followed for clinical events after one year by hospital records, follow-up visits or telephone contact. At the most recent follow-up, no patients had Class IV angina, and only three (11.5%) had Class II angina, while the remaining had Class I or II angina. Compared to baseline, average angina class decreased from 3.6 ± 0.5 to 1.3 ± 1.0 after the first year. This benefit persisted to 24 months when the mean angina class was 1.5 ± 1.2 (p< 0.05).
Major clinical events such as death, myocardial infarction (MI, or heart attack) and repeat revascularization were uncommon during the first year but more frequent after one year at a rate consistent with the severity of the underlying disease in a population with advanced atherosclerosis. The majority of events were the result of progression of disease in areas of the heart remote from the site of injection.
Previous Clinical Data
Physicians who participated in the Phase I study published previous reports stating that the results demonstrated the safety of VEGF-2 and citing significant improvement in the exercise tolerance time in all dose groups. The study reports reflected that 80% of the patients treated experienced an improvement (decrease) in angina class of two or more levels and 40% of the patients experienced complete elimination of angina symptoms. Similarly, significant reductions in the number of angina episodes per week and the number of nitroglycerin tablets taken were observed. Given the invasive nature of this trial, there was not a control group that received a placebo.
The Phase I trial was followed by a Phase I/IIa trial in which 19 patients were treated in a double-blinded, placebo-controlled study where VEGF-2 was injected via a cardiac catheter. This Phase I/IIa trial showed an average increase of almost two minutes of the exercise tolerance time in the VEGF-2 treated patients, and significant decrease in angina class in 50% of patients in the high dose VEGF-2 group.
About the Technology
VEGF-2 is a growth factor that is believed to promote the development of supplemental collateral blood vessels, a process known as therapeutic angiogenesis. In the Phase IIb trial (GENASIS) for severe angina, VEGF- 2 is delivered to the ischemic heart muscle in the form of "naked" plasmid DNA, a non-viral delivery vector. Once administered, the DNA plasmid appears to be taken up and expressed by myocardium near the injection site. Inside the cell, the DNA plasmid then enters the nucleus of the cell without a requirement of incorporation into the genomic DNA. The Phase IIb clinical trial expects to see the effect of the expression of DNA-encoded VEGF-2, which in turn stimulates the growth of new blood vessels by promoting the migration and proliferation of endothelial cells in the heart.
Coronary Artery Disease
In its most recently published data regarding cardiovascular disease in the United States, the American Heart Association reports cardiovascular disease is the leading cause of death representing approximately 38% of all deaths in 2002. Further, cardiovascular disease claims more lives each year than the next five leading causes of death combined. The American Heart Association estimates that 54% of all deaths from cardiovascular disease are attributable to coronary artery disease.
Coronary artery disease is a condition characterized by a narrowing of the coronary arteries and reduced blood flow, and therefore oxygen, to the heart. The lack of blood flow and oxygen to an organ is referred to as ischemia, and myocardial ischemia refers to the lack of blood flow and oxygen to the heart muscle. The American Heart Association estimates that more than 13 million Americans have coronary artery disease.
The primary symptoms of coronary artery disease and myocardial ischemia include heart attack and angina, the medical term for chest pain or discomfort due to myocardial ischemia. Class III angina is characterized by a marked limitation of ordinary physical activity. The most severe class of angina, Class IV, is characterized by an inability to carry on any physical activity without discomfort.
The American Heart Association estimates that approximately 6,400,000 coronary patients in the United States have angina. Of these patients with angina, approximately 150,000 to 250,000 (Class III and IV angina) coronary artery disease patients annually are considered refractory, which means they cannot be successfully treated with conventional cardiovascular therapies. In most cases, these patients have undergone multiple invasive procedures and/or surgeries that have been unsuccessful. Corautus has targeted this critical patient population as the initial candidates for its VEGF-2 gene therapy treatment.
About Blackwell Publishing
Blackwell Publishing is the world's leading society publisher, partnering with more than 600 leading academic and professional societies. Blackwell publishes The Journal of Interventional Cardiology, along with over 750 journals and 600 text and reference books annually, across a wide range of academic, medical, science and professional subjects.
About Corautus Genetics Inc.
Corautus Genetics Inc. is a clinical-stage biopharmaceutical company dedicated to the development of gene transfer therapy products for the treatment of severe cardiovascular and peripheral vascular disease. Corautus is currently developing and testing a gene transfer product using the Vascular Endothelial Growth Factor-2 (VEGF-2) gene to promote therapeutic angiogenesis in ischemic muscle for the relief of severe angina. In July 2003, Corautus entered into a strategic alliance with Boston Scientific Corporation (NYSE:BSX) to develop, commercialize and distribute the VEGF-2 gene therapy products. For more information, please visit http://www.
This press release may contain forward-looking statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Such statements are subject to certain factors, risks and uncertainties that may cause actual results, events and performances to differ materially from those referred to in such statements. These risks include statements which address operating performance, events or developments that we expect or anticipate will occur in the future, such as projections about our ongoing clinical trial, the potential benefits from previous clinical trials, sufficient enrollment of suitable patients in our clinical trial, future results of operations or our financial condition, adequacy of funding, benefits from the alliance with Boston Scientific, research, development and commercialization of our product candidates, anticipated trends in our business, manufacture of sufficient and acceptable quantities of our proposed products, approval of our product candidates, meeting additional capital requirements, and other risks that could cause actual results to differ materially. These risks are discussed in Corautus Genetics Inc.'s Securities and Exchange Commission filings, including, but not limited to, the risk factors in Corautus' Annual Report on Form 10-K for the year ended December 31, 2003 filed March 30, 2004, which are incorporated by reference into this press release.
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