Acute Myocardial Infarction
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 2012 Statistical Update, there were approximately 935,000 cases of myocardial infarction that occurred in the United States in 2008 and approximately 7.9 million individuals living in the United States that had previously suffered a heart attack. In addition, there were approximately 812,000 deaths that occurred from all forms of cardiovascular disease, including 462,000 individuals that died as a result of coronary heart disease and heart failure. 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.
MultiStem has been studied in validated animal models of acute myocardial infarction (AMI) by us and our collaborators, such as 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.
In 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 to 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 included 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 2010, we announced top line results from the 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, and:
- 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); and
- 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 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 four months, showing a consistent safety profile and meaningful improvement in multiple clinical parameters, including LVEF, stroke volume, wall motion and other parameters.
We have completed preliminary planning for a 150 patient Phase 2 trial that has been authorized by the FDA. Working alone or in conjunction with a partner, we intend to advance this program into further clinical development as resources permit.