CARLSBAD, Calif., April 27 /PRNewswire-FirstCall/ -- Isis Pharmaceuticals, Inc. today announced results of a study showing that ISIS 301012 reduced atherosclerotic plaques, apoB-100, and circulating inflammatory cytokines in an animal model of atherosclerosis. These data support a growing body of evidence demonstrating that ISIS 301012 has the potential to treat patients with coronary artery disease. Isis recently reported in a Phase 2 trial that ISIS 301012 produced rapid, dose-dependent and prolonged reductions of its target, apoB-100, with concomitant reductions in low density lipoprotein (LDL or "bad" cholesterol), very low density lipoprotein (VLDL), total cholesterol and triglyceride levels in patients with high cholesterol. ISIS 301012 is a second-generation antisense drug that inhibits the expression of apoB-100, a protein critical to the formation and transport of the "bad" cholesterol particles involved in heart disease -- LDL and VLDL. Rosanne Crooke, Ph.D., Director of Cardiovascular Research of Isis Pharmaceuticals, presented these data at the Arteriosclerosis, Thrombosis and Vascular Biology (ATVB) meeting in Denver, Colorado.
ISIS 301012 was administered to mice that were bred to contain no LDL receptor. These transgenic mice also expressed human apoB-100. In this transgenic model, mice develop extensive atherosclerotic plaques. A 14-week treatment with ISIS 301012 produced a dose-dependent reduction in apoB-100 levels, with concomitant decreases in aortic plaque volume. At 50 mg/kg/wk, ISIS 301012 treatment reduced the levels of apoB-100 by 69% (p<0.001) and aortic plaque volume by 75% (p=0.033) compared to control-treated mice. In addition, ISIS 301012 also substantially reduced circulating inflammatory cytokines, including interferon-gamma (INF-gamma), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha). ISIS 301012 is being developed by Isis as part of its recently announced collaboration with Symphony GenIsis.
"Reducing atherosclerotic plaques in animals confirms that ISIS 301012 has the potential to benefit patients who already have atherosclerosis," said Dr. Crooke. "Patients suffering from cardiovascular disease often have high cholesterol, which leads to hardening of the arteries, or atherosclerotic plaques, increasing their risk of heart attack and stroke."
"In Phase 2 studies, we have demonstrated that ISIS 301012 reduces all atherogenic lipids, including LDL and triglycerides, in patients with high cholesterol, which suggests that ISIS 301012 could be the first lipid lowering drug with statin-like reductions in LDL that also significantly reduces triglycerides, an additional risk factor for coronary artery disease," Dr. Crooke added. "We believe that ISIS 301012 has the potential to help patients reach their targeted cholesterol levels and combat cardiovascular disease, a leading cause of death worldwide."
ABOUT ISIS 301012
ISIS 301012 is a second-generation antisense drug that inhibits apoB-100, a protein critical to the synthesis and transport of the "bad" cholesterol involved in heart disease -- low density lipoprotein cholesterol (LDL) and very low density lipoprotein (VLDL). Lowering cholesterol and triglyceride levels is a key component in the prevention and management of cardiovascular disease.
Development plans for ISIS 301012 include the rapid development of the drug for patients with familial hypercholesterolemia (FH), a genetic disorder that causes extremely high cholesterol levels and results in the early onset of heart disease. ISIS 301012 has the potential for an accelerated pathway to commercialization because of the unmet medical need in this desperate patient population. Additional trials have been designed to address the larger commercial market represented by the traditional population of patients with high cholesterol who are still not reaching their targeted cholesterol levels.
In September 2005, Isis initiated the Phase 2 development program of ISIS 301012. Phase 2 trials of ISIS 301012 are being conducted in patients with high cholesterol. Isis is continuing its Phase 2 single-agent trial using higher dosing (300 and 400 mg/wk) of ISIS 301012 in patients with high cholesterol. Isis is also conducting a Phase 2 trial of ISIS 301012 in combination with statin therapy in patients with high cholesterol. Isis is also conducting Phase 2 studies of ISIS 301012 in FH.
Isis recently reported initial data from the low-dose cohorts of a Phase 2 clinical trial of ISIS 301012 as a single-agent in patients with high cholesterol. ISIS 301012 produced rapid, dose-dependent and prolonged reductions of its target, apoB-100, with concomitant reductions in LDL, VLDL, total cholesterol and triglyceride levels in patients with high cholesterol. In Phase 1 trials, ISIS 301012 produced rapid, dose-dependent and prolonged reductions of its target, apoB-100, with concomitant reductions in LDL, VLDL, total cholesterol and triglycerides in normal subjects with elevated cholesterol. In a drug-drug interaction study, ISIS 301012 did not interact with simvastatin or ezetimibe, currently available lipid lowering drugs with which ISIS 301012 may be dosed in combination. Additionally, the drug has been well tolerated.
ABOUT CHOLESTEROL AND CARDIOVASCULAR DISEASE
According to the American Heart Association, an estimated 107 million American adults have total blood cholesterol values of 200 mg/dL and higher, and of these about 38 million American adults have levels of 240 or above. In adults, total cholesterol levels of 240 mg/dL or higher are considered "high risk". Levels from 200 to 239 mg/dL are considered "borderline-high risk". Low-density lipoprotein, or LDL, known as the "bad" cholesterol, can clog arteries, increasing the risk of heart attack and stroke.
According to the World Health Organization (WHO), heart disease and stroke kill 17 million people a year, which is almost one-third of all deaths globally. By 2020, the WHO projects that heart disease and stroke will become the leading cause of both death and disability worldwide, with the number of fatalities projected to increase to over 20 million a year and by 2030 to over 24 million a year.
Familial hypercholesterolemia is a dominantly inherited genetic condition that results in markedly elevated LDL (low-density lipoprotein) cholesterol levels beginning at birth, and resulting in heart attacks at an early age. Affected people have consistently high levels of low-density lipoprotein, which leads to premature atherosclerosis of the coronary arteries.
ABOUT ISIS' SYMPHONY GENISIS COLLABORATION
In April 2006, Isis entered into a collaboration with Symphony Capital Partners, L.P. and a group of co-investors to form Symphony GenIsis, Inc., capitalized with $75 million, to fund the development of Isis' cholesterol-lowering drug, ISIS 301012, and two novel drugs from Isis' metabolic disease program. Isis licensed to Symphony GenIsis the intellectual property for its apoB-100, glucagon receptor and glucocorticoid receptor programs. The financing will support Isis' development of ISIS 301012 through the completion of registration-supporting clinical studies in patients with familial hypercholesterolemia and the completion of Phase 2b clinical trials in patients with high cholesterol. The financing will also support Isis' development of two novel diabetes drugs through initial proof of concept in human clinical trials. In addition to providing the financial support to move these drugs forward aggressively, the transaction allows Isis to continue to control and manage the development of ISIS 301012 and two other potentially valuable drugs through key development milestones.
ABOUT ISIS PHARMACEUTICALS, INC.
Isis is exploiting its expertise in RNA to discover and develop novel drugs for its product pipeline and for its partners. The Company has successfully commercialized the world's first antisense drug and has 15 drugs in development. Isis' drug development programs are aimed at treating cardiovascular, metabolic and inflammatory diseases. Isis' partners are focused in disease areas such as inflammatory, ocular, viral and neurodegenerative diseases, and cancer. In its Ibis division, Isis is developing and commercializing the IBIS biosensor system, a revolutionary system to identify infectious organisms. As an innovator in RNA-based drug discovery and development, Isis is the owner or exclusive licensee of approximately 1,500 issued patents worldwide. Additional information about Isis is available at www.isispharm.com.
This press release includes forward-looking statements regarding the development, therapeutic potential and safety profile of ISIS 301012 for the treatment of high cholesterol and cardiovascular disease. Any statement describing Isis' goals, expectations, intentions or beliefs is a forward-looking statement and should be considered an at-risk statement, including those statements that are described as Isis' goals. Such statements are subject to certain risks and uncertainties, particularly those inherent in the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such products. Isis' forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause its results to differ materially from those expressed or implied by such forward-looking statements. Although Isis' forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known by Isis. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Isis' programs are described in additional detail in Isis' annual report on Form 10-K for the year ended December 31, 2005, which is on file with the U.S. Securities and Exchange Commission (SEC) and available from the Company.
Isis Pharmaceuticals, Inc.CONTACT: Corporate Communications, Navjot Rai of Isis Pharmaceuticals,Inc., +1-760-603-2331
Web site: http://www.isispharm.com/
