Scimitar Equity Blog

ATHX announced positive (7/28/10) results from its phase I clinical trial of MultiStem^(R), its allogeneic cell therapy product, administered to individuals following acute myocardial infarction (AMI), more commonly referred to as a heart attack. 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.

The phase I clinical trial is 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 catheter into the damaged region of the heart 2-5 days following percutaneous coronary intervention (PCI), a standard treatment for heart attack,
• 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,
• 19 treated and 6 registry subjects participated in the study,
• The trial is being conducted at cardiovascular treatment centers in the U, including the Cleveland Clinic, Columbia University Medical Center and Henry Ford Health System.

Highlights of the Study:

• 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.

During the first 24 hours following MultiStem administration, patients were assessed for infusion-related toxicity and other acute adverse events. Subsequently, patients were evaluated for cardiac adverse events.

• The primary endpoints for the study were the assessment of acute adverse events during the first 24 hours following administration, post-acute adverse events up to 30 days, and catheter-related events,
• The administration of MultiStem was found to be well tolerated at all dose levels evaluated,
• There were no dose limiting toxicities associated with the administration of MultiStem,
• Immediately following dosing, there were no clinically significant changes to vital signs or evidence of allergic reaction associated with MultiStem administration,
•  Over the 30-day post-acute observation period, no infusional toxicities or clinically significant cardiac adverse events deemed to be definitely related to MultiStem occurred.

MultiStem had a favorable safety profile over the four-month period following treatment. There was no dose dependent effect of MultiStem on adverse events (AEs) and generally AEs were mild to moderate in nature. Overall, there were several observed AEs characterized as potentially related to MultiStem or catheter delivery. These were generally mild to moderate in nature and were not dose dependent.

While the primary objective of this phase I study is to evaluate the safety of MultiStem administered to AMI patients, echocardiogram data are being collected and evaluated for evidence of efficacy signals to facilitate planning for subsequent clinical studies, noting importantly that the study was not powered for efficacy endpoints.

• Specifically, following a heart attack, patients were screened by left ventriculogram and/or echocardiogram, analyzed at the clinical site, to determine if their LVEFs met inclusion criteria (30 to 45). Prior to MultiStem administration (and between 2-5 days following PCI for registry patients), an additional echocardiogram was performed, which served as the baseline for subsequent analysis.

Additional echocardiogram data were collected at prescribed time points according to the protocol. Echocardiogram data collected for each patient were blinded, and evaluated at a central facility.

• The preliminary echocardiogram data demonstrated that each group had improvement in mean LVEF at four months compared to mean baseline LVEF,
• Patients receiving 20, 50, or 100 million MultiStem cells demonstrated absolute improvements in mean LVEF at 4 months of 5.2, 9.8 and 1.5 % points; compared to an absolute improvement of 1.1 % points in the registry group,
• Although the study was not powered for efficacy endpoints, patients in the medium dose group exhibited a statistically significant improvement in LVEF over mean baseline for that group, 9.8 percentage points (p<0.02), representing a 23.4% improvement over baseline,
• The improvement in mean LVEF for each group compared to the registry group, though meaningful, was not statistically significant.

Notably, several patients in the high dose group exhibited substantially higher baseline LVEFs than their initial screening LVEFs, which created a higher baseline mean for that patient group.

• Including only patients whose baseline LVEFs <= 45, the absolute improvements in mean LVEF were 3.9, 13.5 and 10.9 % points for the 20, 50, or 100 million dose groups, respectively, compared to an absolute improvement of 0.9 % points in the registry group,
• Among these patients (i.e., LVEFs <= 45), those in both the medium and high dose groups exhibited a substantial increases in LVEF, representing more than 25% improvements relative to baseline LVEF for those patient groups,
• Additional analysis of the echocardiogram data is ongoing, and we will evaluate possible effects on other measures of heart function.

These preliminary phase I MultiStem results are consistent with the results obtained in preclinical studies and compare favorably to the results from other cell therapy treatments for AMI. This suggests that MultiStem could have a meaningful impact on improving heart function following heart attack.