Transendocardial delivery of ixmyelocel-T, a bone marrow-derived cellular therapy, reduced clinical cardiac events when compared with placebo in patients with symptomatic heart failure (HF) due to ischemic dilated cardiomyopathy. This led to improved patient outcomes, researchers observed.
Timothy D. Henry, MD, of Cedars-Sinai Heart Institute, Los Angeles, presented the IxCELL-DCM trial findings at the 2016 American College of Cardiology Scientific Sessions & Expo (ACC), which were simultaneously published in Lancet.
Dr Henry said during an ACC press conference that regenerative therapies, like bone marrow-derived cellular therapy, are an attractive approach in HF, but noted that earlier research utilized unselected bone marrow.
“The problem with unselected bone marrow is that as we get older, the number of our stem cells and potency of those cells decline,” Dr Henry said, adding that this resulted in excellent safety in those trials but “only modest efficacy, so it stimulated … a new generation of cell therapies.”
In the present randomized, double blind, placebo-controlled phase 2b trial, researchers tested an autologous, bone marrow-derived, multicellular therapy called ixmyelocel-T in 126 patients from 31 sites in North America between April 2, 2013 and January 28, 2015. All patients had New York Heart Association class III or IV symptomatic HF due to ischemic dilated cardiomyopathy, left ventricular ejection fraction (LVEF) ≤ 35%, an automatic implantable cardioverter defibrillator, and were ineligible for revascularization procedures.
Dr Henry and colleagues randomly assigned patients on a 1:1 ratio to receive either ixmyelocel-T (n=66) or placebo (n=60) at the time of bone marrow aspiration and followed patients for 12 months. Both groups underwent a bone marrow biopsy and intramyocardial injection.
A composite of all-cause death, cardiovascular admission to hospital, and unplanned clinic visits to treat acute decompensated heart failure served as the primary end point.
Results of the primary efficacy analysis indicated that in the placebo group, 50 events occurred in 49% of the patients, whereas 38 events occurred in 38% of the ixmyelocel-T group (risk ratio:0.63; 95% confidence interval, 0.42-0.97; P=.0344).
In further analysis, more patients in the placebo group experienced a serious adverse event compared with the ixmyelocel-T group (75% vs 53%; P=.0197).
Cause for ‘Cautious Optimism’
In an interview with Cardiology Advisor, study investigator Catalin Toma, MD, of the University of Pittsburgh Medical Center Heart and Vascular Institute, said that the findings are very encouraging for the field of cell therapy and that, overall, he is cautiously optimistic about the approach.
“The trial was well executed, in particular with the inclusion of a true placebo arm,” he said. “Furthermore, this trial demonstrated an impact in clinically significant hard end points, as opposed to structural end points used in prior studies.”
However, Dr Toma noted that the results were not consistent across the board, with no differences observed in functional class, ejection fraction, or walking distance.
“Although this is somewhat surprising, it may reflect the heterogeneity of the patients enrolled in the study with regards to the amount of viable myocardium at baseline,” he said.
A Promising Interventional Approach
Going forward, Dr Toma said that he hopes the results of the trial will encourage physicians to seek out sites enrolling in cells therapy trials and think about this option for their patients.
“Provided cell therapy will be validated in larger phase 3 trials, this will be an additional tool in the emerging field of interventional therapies for heart failure,” he said.
- Henry TD, Quyyumi AA, Schaer GL, et al. Late-Breaking Clinical Trials V. The IxCell-DCM trial: transendocardial injection of Ixmyelocel-T in patients with ischemic dilated cardiomyopathy. Presented at the 65th Annual Scientific Sessions and Expo of the American College of Cardiology. April 2-4, 2016; Chicago, IL.
- Patel AN, Henry TD, Quyyumi AA, et al; for the ixCELL-DCM Investigators. Ixmyelocel-T for patients with ischaemic heart failure: a prospective randomised double-blind trial. Lancet. 2016. doi:10.1016/s0140-6736(16)30137-4.