Overview
Despite recent advances in cardiovascular care, myocardial infarction remains one of the leading causes of death and disability in the United States. Myocardial infarction is caused by the blockage of one or more arteries that supply blood to the heart, resulting in significant injury to the heart muscle that severely affects the patient's quality of life, or causes death. Such blockages can be caused, for example, by the rupture of an atherosclerotic plaque. According to the American Heart Association 2010 Statistical Update, there were approximately 935,000 cases of myocardial infarction that occurred in the United States in 2006, approximately 8.5 million individuals living in the United States that had previously suffered a heart attack, and 17.6 million individuals with heart disease. In addition, there were more than 425,400 deaths that occurred from various forms of coronary heart disease, and 141,500 deaths due directly to myocardial infarction in 2006. A variety of risk factors are associated with an elevated risk of myocardial infarction or atherosclerosis, including age, high blood pressure, smoking, sedentary lifestyle, and genetics. While advances in the diagnosis, prevention, and treatment of heart disease have had a positive impact, there is clearly room for improvement – myocardial infarction remains a leading cause of death and disability in the United States and the rest of the world.
Our Approach
MultiStem is a proprietary biologic therapy that consists of a special class of human stem cells obtained from adult bone marrow or other non-embryonic tissue sources. In contrast to other stem cell types, which typically cannot be expanded to a substantial degree, material from a single qualified donor may be used to produce hundreds of thousands or even millions of clinical doses of MultiStem, which are extensively characterized to ensure product consistency and safety. MultiStem may be produced on a large scale for future clinical use and stored in frozen form until needed.
MultiStem has great potential as a “best-in-class” cell therapy based on its ability to deliver therapeutic benefit through multiple mechanisms of action, its ability to be delivered “off-the-shelf” like a pharmaceutical product and its consistent safety profile. In pre-clinical and clinical studies we have evaluated the delivery of MultiStem directly to the region of ischemic damage in the heart using a micro-infusion catheter delivery system. This system enables rapid and efficient placement of MultiStem.
MultiStem has been studied in validated animal models of acute myocardial infarction at both the Cleveland Clinic and the University of Minnesota. Investigators demonstrated that the administration of allogeneic MultiStem into the hearts of animals damaged by experimentally induced heart attacks resulted in significant functional improvement in cardiac output and other functional parameters compared with animals that received placebo or no treatment. Further, the administration of immunosuppressive drug was not required and provided no additional benefit, and supports the concept of using MultiStem as an allogeneic product.
Clinical Development Progress to Date
In February, 2010 we announced successful completion of enrollment of a company-sponsored multicenter Phase I clinical trial to evaluate the safety of MultiStem administered via catheter to patients who have suffered an acute myocardial infarction, commonly referred to as a heart attack. The phase I clinical trial was an open label, multi-center dose escalation trial evaluating the safety and maximum tolerated dose of a single administration of allogeneic MultiStem cells following an AMI. Enrolled patients received MultiStem delivered via a micro-infusion catheter into the damaged region of the heart 2-5 days following percutaneous coronary intervention (PCI), a standard treatment for heart attack that typically involves balloon angioplasty and insertion of stents to reperfuse ischemic tissue and restore blood flow.
The study includes patients in three treatment cohorts or dose groups (20 million, 50 million and 100 million cells per patient) and a registry group where patients received only standard of care (e.g. PCI). Nineteen treated and six registry subjects participated in the study. The trial was conducted at cardiovascular treatment centers in the United States, including the Cleveland Clinic, Columbia University Medical Center and Henry Ford Health System.
In the third quarter, 2010 we announced top line results from the ongoing Phase I study. The study results, based on four months of post-treatment patient data, demonstrate that MultiStem was well tolerated at all dose levels and also suggest improvement in heart function in treated patients. Highlights of the study include the following:
Administration of MultiStem was found to be well tolerated at all dose levels
- No clinically significant changes in vital signs, allergic reactions, or infusion-related toxicities were associated with MultiStem administration
- Each dose group showed improvement in mean left ventricular ejection fraction (LVEF), a measure of heart function, compared to baseline and relative to the registry group
- Patients in the 50 million dose group had a statistically significant absolute improvement in mean 4-month LVEF relative to baseline (9.8 percentage points, representing a 23.4% improvement over baseline, p<0.02)
- Among patients with more severe heart attacks – as measured by baseline LVEFs less than or equal to 45% – the 50 and 100 million dose groups each demonstrated better than a 25% improvement in mean LVEF at 4 months post treatment over baseline
These study results were published on-line in the journal Circ Research in November, 2011, and in the print issue in January 2012.
In June, 2011 the lead investigator for the study, Dr. Marc Penn, presented one-year follow up data at the Eighth International Symposium on Stem Cell Therapy and Cardiovascular Innovations. These results confirmed and extended the previous clinical observations at 4 months, showing a consistent safety profile, and meaningful improvement in multiple clinical parameters, including LVEF, stroke volume, wall motion, and other parameters.
For additional information regarding this study, see the press release summarizing the top line results at http://ir.athersys.com/releases.cfm or please contact the company.
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