Aastrom uses a cell-processing manufacturing technology to expand naturally occurring populations of cells derived from the patient’s own bone marrow. Source: Aastrom Biosciences

LAS VEGAS—The late-breaking CATHETER DCM trial, presented May 10 at the 35th annual meeting of the Society for Cardiovascular Angiography and Interventions (SCAI), showed some trends toward progress for bone marrow stem cells to improve heart function in some patients with progressive heart failure due to dilated cardiomyopathy. However, principal investigator Timothy D. Henry, MD, of the Minneapolis Heart Institute at Abbott Northwestern Hospital, explained the results in the context of cell therapy for multiple cardiac conditions.

“There is currently a lot of misunderstanding about cell therapy,” said Henry during a press conference. “On the one hand, the lay media has focused primarily on embryonic stem cells and its ethical controversy, which is not really an issue anymore because the ongoing U.S. trials in humans are only using adult stem cells.”

Secondly, he pointed to the wide and disparate spectrum of cell therapy research in the U.S. and internationally—from the basic science community who are not looking to transition to assessment in humans to some having adipose cells available in local shopping malls for cosmetic purposes in certain foreign countries.

“Both of these extremes can be equally damaging to the field,” he said. “Stem cell therapy, like all other medical therapies, should be assessed for risk-benefit profile. We should be examining at the relative risk-benefit ratio of the cell itself for the condition that we are attempting to treat.

“Fortunately, in cardiology, this risk-benefit analysis is where we currently stand.”

However, he also acknowledged some negative sentiment about the therapy, due to “perceived lack of rapid progress." Refuting those claims, Henry said that “in a relatively short period of time, large, Phase 3 trials have been initiated for acute MI, refactory angina, critical limb ischemia and heart failure.”
 
This Phase 2b trial enrolled 22 ischemic dilated cardiomyopathy (IDCM) and non-ischemic (NIDCM) patients with New York Heart Association (NYHA) HF Class III/IV and a left ventricular ejection fraction (LVEF) of less than 30 percent who had limited treatment options. In fact, the average LVEF in both was 22 percent. The patients were randomized 2:1 to ixmyelocel-T or control and followed for 12 months.

After the bone marrow aspirate cells were extracted, they were cultured in an automated system (Aastrom Biosciences) for 12 days, expanding the number of alternatively activated macrophages and mesenchymal cells, while retaining many of the cell types of the original bone marrow.  Specifically, Ixmyelocel-T is developed to increase the numbers of immune cells including macrophages and monocytes, as well as mesenchymal cells, stem cells that can differentiate into several different cell types.

The resulting cell treatment is then injected into the patient’s heart muscles to encourage growth of new tissue and improve inflammation, according to Henry, adding that this process produces an “enhanced product.” After this 12-day enhancement process, the cells were percutaneously delivered to the heart with an intramyocardial injection using the Myostar Injection Catheter after Noga XP cardiac mapping (Biosense Webster).

At 12 months, the researchers reported no procedural complications and no difference in adverse events in the treated vs. control patients. IDCM ixmyelocel-T treated patients had improved clinical outcomes with a mean number of major adverse cardiovascular events of 0.22 compared with 1.67 in control patients. Also, more IDCM ixmyelocel-T treated patients had improvements in NYHA Class, six minute walk distance and ejection fraction compared with control or NIDCM patients.

Henry stressed that ischemic patients responded better to the therapy.

“Treatment with ixmyelocel-T was well-tolerated and patients who received the cell therapy showed improved symptoms after one year,” said Henry. “The results provide a strong basis for a larger clinical trial of this treatment in patients with dilated cardiomyopathy.”

While the study trended positively, its results were not statistically significant and the study was hindered by its small size; however, in the context of cardiac stem cell research, Henry posited another rosy image if ongoing Phase 3 trials produce positive outcomes in the next year to two. “This very new potential therapy has made great strides in a relatively short period of time,” he said.

Later this summer, a larger Phase 3 trial will begin with this cell for this patient population. Likely, two Phase 3 trials will be needed before FDA approval might be granted. 

Aastrom Biosciences sponsored the study.