Reed Miller

May 11, 2012

May 11, 2012 (Las Vegas, Nevada) — Dilated cardiomyopathy (DCM) patients may benefit from the injection of ixmyelocel-T (Aastrom Biosciences, Ann Arbor, MI), a derivative of autologous bone-marrow cells, a small study shows [1].

Here at the Society for Cardiovascular Angiography and Intervention (SCAI) 2012 Scientific Sessions, Dr Tim Henry (Minneapolis Heart Institute, MN) presented results of the 22-patient Catheter DCM phase 2a trial of the ixmyelocel-T therapy. Previous preclinical and clinical studies have shown that myocardial repair with unselected bone-marrow mononuclear cells is safe but that the number and potency of autologous stem cells from unselected bone marrow decrease with age and risk factors. For example, the FOCUS trial, comparing injections of bone-marrow mononuclear cells with placebo in the treatment of left ventricular dysfunction and angina, showed no overall improvement in maximum VO2 or end systolic volume but significant improvement in left ventricular ejection fraction (LVEF), and the clinical benefits were directly related to cell function and type.

All of the patients in the Catheter DCM trial had NYHA class 3 or 4 heart failure with an LVEF ≤30% and limited treatment options. They were stratified by ischemic or nonischemic status and randomized 2:1 to ixmyelocel-T injections or standard of care and followed for a year.

Ixmyelocel-T is created by aspirating the patient's bone-marrow cells and culturing them for 12 days to expand the number of alternatively activated macrophages and mesenchymal cells. In the treatment group, the cells were injected into the myocardium.

There were no procedural complications and no difference in adverse events, including arrhythmias, in the treatment vs control groups, but ischemic ixmyelocel-T–treated patients had an average of 0.22 major adverse events per patient compared with 1.67 in the control patients. Ischemic ixmyelocel-T–treated patients showed improvements in NYHA class, six-minute-walk distance, and ejection fraction compared with controls and the nonischemic patients treated with ixmyelocel-T.

"The effects on ejection fraction are modest. I think that if we honestly interpret these results, where we're at with cell therapy right now is that we do a good job of growing new blood vessels," Henry said. "So to the extent these are ischemic cardiomyopathy patients who need improved blood supply, we can improve their symptoms and we're doing very well with refractory angina and critical ischemia, but we're still a long way away from growing new heart muscle."

Based on the results of the Catheter DCM trial, later this summer the investigators will begin a phase 2b study of ixmyelocel-T in ischemic DCM patients with LVEF ≤35%, Henry said.

Commenting on the study, Dr James Hermiller (St Vincent's Hospital, Indianapolis, IN) said, "The fastest-growing part of our cardiac service line is advanced heart failure . . . and I suspect that, as time goes on, interventionalists are going to be more and more involved and interfacing with the care of these patients, whether it's transcatheter [ventricular assist devices] VADs or cell therapy, etc. You can see this growing in the next five to 10 years."

Henry agreed that interventionalists will get more involved in heart-failure treatment. "This trial and every other trial we've done have enrolled extremely fast, because there's a huge number of these patients out there who have class 3 heart failure despite optimal medical therapy or device therapy — which should come first, clearly — but who aren't sick enough or a good candidate for a ventricular assist device or transplant, which are much more expensive and much more physician and nurse 'heavy' in terms of resources," Henry said.

This trial was sponsored by Aastrom. Henry also receives research support for other cell-therapy trials from the National Institutes of Health, Baxter, and Angioblast.