A Phase 2 Trial of AMI MultiStem® Therapy in Subjects With Non-ST Elevation Acute Myocardial Infarction (MI-NSTEMI)


Cardiovascular disease is an area of significant clinical need and its prevalence is expected to grow in the years ahead. Despite treatment advances in recent years, cardiovascular disease remains the leading cause of death, and represents one of the leading causes of disability around the world. The number of acute myocardial infarctions (AMI) is expected to increase, primarily as a result of the aging population, and may not fully reflect the impact of the dramatic escalation in obesity rates that has occurred for both adults and children in recent years, which could further exacerbate the long-term challenges and increase costs associated with cardiovascular disease and other conditions.

MultiStem has been studied in validated animal models of AMI by us and our collaborators. 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.


Phase I AMI Data


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.

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 cell therapy 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 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 tolerability profile and meaningful improvement in multiple clinical parameters, including LVEF, stroke volume, wall motion and other parameters.

We were conducting a Phase 2 clinical trial evaluating the administration of MultiStem Cell Therapy to patients who have suffered an AMI, but due to challenges in the conduct of the study, we have suspended further enrollment at this time.